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Biomedical subjects

J Lecomte

Publications and source records attributed to J Lecomte.

At least 37 records · Page 2Linked to original sources
PubMed1996

Prognostic factors for response to chemotherapy containing platinum derivatives in patients with unresectable non-small cell lung cancer. (NSCLC).

PURPOSE: To identify pretreatment variables predicting response to platinum derivatives containing chemotherapy in patients with unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients included in one of the 7 consecutive clinical trials conducted by the European Lung Cancer Working Party between December 1980 and August 1991. All patients received a cisplatin or carboplatin containing chemotherapy. We analyzed 22 potential prognostic factors including sex, age, histology, performance status, weight loss, type of lesions, extent of disease, main metastatic sites and several biological parameters, namely white blood cell count (WBC), neutrophil count, platelet count, hemoglobinemia, creatininemia, serum alkaline phosphatases and LDH. RESULTS: On 1052 eligible patients. 107 were not assessable for response. The objective response rate was 26% (95% C.I.: 23, 29%). Univariate analysis identified as statistically significantly associated with a higher objective antitumoral response rate the following characteristics: a normal platelet count, the absence of skin metastasis, the absence of adrenal metastasis, a higher creatininemia, a normal hemoglobinemia, an older age and a normal WBC count. On a restricted set of variables including data from 777 patients, a multivariate logistic regression model disclosed age and platelet count as significantly and independently related to response rate. CONCLUSION: Clinical and demographic characteristics of patients with unresectable NSCLC, as well as routine laboratory parameters, could not accurately predict response to chemotherapy in a population of patients selected for a clinical trial. Future studies on this subject should include more sophisticated variables as new biomolecular makers.

Adult↗
PubMed1996

Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE AND METHODS: The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin). RESULTS: Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival. CONCLUSION: We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.

Adult↗
PubMed1996

[Nonnius and the Spa cure].

The 12th of July 1635, Jan van Beverwyck wrote a letter from Dordrecht to his esteemed friend Luis Nunez, in Antwerp. He asked him for indications about the cure of kidney stones of which he was suffering. He had just passed two calculi very painfully. Nunez answered on July 31. His letter summarized his own experience with this disease. In such cases, temperate diuretics and emollients are well indicated: ingestion of light decoctions of Malva and Viola, Caerefolium and Parieteria as well as Marshmallow syrup. No purge and no 'chemicals'. However, the best remedy was drinking Spa water. Usually the best way to absorb it is to come to the springs, in the Ardennes, part of the independent Principality of Liège. However, considering the horrors of the war (the Thirty Years War) endangering the country, van Beverwyck would be wise to drink imported water during 40 or 50 days, while staying home quietly, in Dordrecht. The letter points out the importance of provoked diuresis in the treatment of kidney stones. On the other hand the letter is an illustration of the continuing contacts between the United Provinces and the Spanish territories and of the commercial traffic between Antwerp, Dordrecht and Spa. The exported water was bottled from many 'pouhons'. It was acid, ferruginous, sulfurous and saturated with carbon dioxide; no pathogen germs, at least at the spring. Nunez quoted the large number of his patients cured with Spa water in Antwerp. This is an illustration of its commercial expansion even during this critical period.

Belgium↗
PubMed1995

Strain variability and localization of important epitopes on the major structural protein (VP2) of infectious pancreatic necrosis virus.

Infectious pancreatic necrosis virus (IPNV), a birnavirus, is an important pathogen in fish farms. Analyses of viral proteins showed that VP2 is the major structural and immunogenic polypeptide of the virus. All neutralizing monoclonal antibodies (mAbs) against IPNV are specific to VP2 and bind to continuous or discontinuous epitopes. In order to determine which parts of the protein are involved in antigenic variations, five IPNV strains were sequenced over the VP2 coding region. Comparison of the sequences obtained with three previously published strains revealed a central variable domain (positions 183 to 335) which encompasses two hydrophilic hypervariable segments. Viral mutants which escaped neutralization were then selected with anti-VP2 mAbs directed against discontinuous epitopes. Sequencing of three mutants revealed a single amino acid mismatch in each of them. All of these substitutions occurred in the hypervariable segments, suggesting that these regions are involved in the formation of a discontinuous epitope. Finally, expression of different truncated VP2s in Escherichia coli allowed localization of the binding site for neutralizing mAbs which recognize continuous epitopes. One of these mAbs bound to the region adjacent to the C-terminus of the variable domain of VP2, while two others reacted with the central and C-terminal parts of the variable domain. No antibody reacted with the N-terminus of VP2. These results suggest that the variable domain of VP2 and the 20 adjacent amino acids of the conserved C-terminal part are the most important in inducing an immune response for the protection of animals.

Amino Acid Sequence↗
PubMed1995

Comparison of the p125 coding region of bovine viral diarrhea viruses.

The p125 (p54/p80) coding region of two cytopathic (CP) strains (Oregon and Singer) and two noncytopathic (NCP) strains (NY-1 and Draper) of bovine viral diarrhea virus (BVDV) were amplified by the polymerase chain reaction, cloned and sequenced. The sequence data confirmed that the two CP strains do not possess any insertion or deletion in their p125 gene as observed in many other CP strains. In the p80, which showed a high amino acid sequence homology among all strains, no amino acid substitution should could be found which distinguished these CP strains from the NCP strains NY-1 and SD-1. Many amino acid substitutions were found in p54 but their individual importance in the CP phenotype is not clear since critical domains of p54 have not yet been experimentally defined. The p54 protein is much less conserved than p80, and sequence homology, as well as dendrogram analysis, permitted us to distinguish two genotypic groups of BVDV (Ia and Ib). The mean homology between strains of these two groups was 77.3/80.4% for the nucleic acid/amino acid sequences while it was 88.0/88.8% and 91.6/93.3% within groups Ia and Ib, respectively. Furthermore, we found that the p125 sequence of our NY-1 strain showed only 92% sequence homology with the partial p80 gene reported for NY-1 but 99.8% homology with another partial sequence of the p125 gene of NY-1 reported elsewhere. These observations underscored the difficulty of maintaining a specific BVDV strain, especially the NCP biotype, in cell cultures.

Amino Acid Sequence↗
PubMed1995

Evidence of a major neutralizable conformational epitope region on VP2 of infectious pancreatic necrosis virus.

A collection of neutralizing monoclonal antibodies (MAbs) produced against the LWVRT 60.1, Jasper and N1 strains of infectious pancreatic necrosis virus (IPNV) were selected for the analysis of VP2 epitopes. Previous characterization of the LW and JA MAbs allowed the identification of continuous and discontinuous epitopes but the topological localization of these sites remained obscure. The ability of these MAbs to differentiate individual epitopes was evaluated by additivity and competition assays using antigen-coated plates and by surface plasmon resonance (SPR), an automated biosensor system that is able to retain the conformation integrity of proteins. IPNV-neutralizing MAbs defined a major, conformational-dependent and immunodominant area where continuous epitopes represent portions of a larger discontinuous epitope. Moreover, weakly neutralizing MAbs could interact with internal sites, located within the foldings of the polypeptide chain. Anti-VP2 MAbs prepared against the European serotype N1 recognized and competed for epitopes present on the North American strain LWVRT 60.1 and Jasper. Attempts to establish the proximity of VP2 and VP3 epitopes have been made by SPR. Results indicate that these major structural proteins do not overlap in the virion.

Antibodies, Monoclonal↗
PubMed1995

Characterization of the small open reading frame on genome segment A of infectious pancreatic necrosis virus.

The genome of infectious pancreatic necrosis virus (IPNV) is composed of two segments of dsRNA. The larger segment contains a small ORF partly overlapping the 5' end of the polyprotein reading frame. Yet very little is known about this possible new gene, which presumably codes for a 17 kDa polypeptide (VP5). The region of the viral genome which encompasses the small ORF was reverse-transcribed and amplified by PCR before cloning and sequencing. Analysis of the sequences obtained from five different virus strains revealed that the small ORF is not found on one of them, and that it is truncated on two others. Moreover, the deduced amino acid sequences did not appear to be well conserved. Despite the large variations between IPNV strains at the genomic level, all predicted VP5 are arginine-rich basic polypeptides. To verify whether the small ORF is translated into protein in fish cells, the 17 kDa polypeptide of the VR-299 strain was expressed as fusion protein in a prokaryotic expression vector and used to produce a specific antiserum. This antiserum reacted with concentrated virus in an immunodot assay indicating that VP5 is synthesized in infected cells, but probably only in small quantities. When tested with 12 other IPNV strains, results were less conclusive than those obtained with strain VR-299. Nevertheless, three of the 12 viruses gave a clearly negative signal in the immunodot assay, suggesting that possibly more than one viral strain lacks the small ORF.

Amino Acid Sequence↗
PubMed1994

Identification of a new group of bovine viral diarrhea virus strains associated with severe outbreaks and high mortalities.

New BVDV strains associated with very high mortalities, which killed about 25% of the veal calves in Quebec in 1993, have been isolated. In this study, characterization of the last two-thirds of the 5' untranslated region (5'UTR) of their genome and virus neutralization experiments with polyvalent antisera raised in different animals both demonstrated that these strains formed a distinct group. Despite a difference of about 25% in the 5'UTR sequence with that of the classical strains, these 5'UTRs maintained the same secondary structure albeit with a higher stability. Serological crossreactivity between the classical and new BVDV strains was relatively low and suggest that new strains should also be included to obtain efficient BVDV vaccines. Based upon the distinct characteristics of these new BVDV strains, we propose to divide BVDV into two groups. Group I comprises the classical BVDV isolates including commonly used laboratory and vaccine strains, and group II comprises the newly described BVDV strains and those associated with thrombocytopenia and hemorrhaging.

Animals↗
PubMed1994

Treatment of tendinitis and bursitis: a comparison of nimesulide and naproxen sodium in a double-blind parallel trial.

The clinical efficacy and the tolerability of nimesulide (100 mg bid) and naproxen sodium (550 mg bid) in the treatment of tendinitis and bursitis were evaluated in a multicentre double-blind study over a 14-day period. Two hundred and five patients were included in the study. Patients randomised to one of two parallel treatment groups. They were clinically examined at days 1, 7 and 14. Blood analysis was performed at day 1 and at the end of the treatment. The main efficacy criterion was the diminution of pain during active mobilisation measured using a visual analogue scale. The improvement of the scores was obvious and similar between the two groups. The secondary efficacy criteria (pain during motion against resistance, functional impairment and global assessment of efficacy) confirmed these favourable results and did not evidence any statistical difference between the two groups. The side effects observed were mainly gastrointestinal. Their frequency and intensity were slightly higher in the naproxen sodium group but without any statistically significant difference (28 complaints in 16 patients in the nimesulide group and 33 complaints in 22 patients in the naproxen group). There was no statistical difference between the two treated groups regarding the general clinical examination and the biological follow-up.

Adult↗
PubMed1993

Comparison of amino acid sequences deduced from a cDNA fragment obtained from infectious pancreatic necrosis virus (IPNV) strains of different serotypes.

Infectious pancreatic necrosis is an important viral disease of salmonid fish reared in hatchery. Its etiological agent, IPNV, showed a high degree of antigenic heterogeneity. Up to 10 serotypes and 2 serogroups were proposed. Yet, very little is known about genomic variations among viruses of different origin. In order to investigate these variations, a 310-bp cDNA fragment was prepared from 17 IPNV strains by reverse transcription of the viral genome and amplification by the polymerase chain reaction. These fragments were then cloned and sequenced. Comparison of the 17 sequences obtained with 3 previously published ones, at the amino acid level, showed that serologically related viruses are highly homologous (over 96% homology) but some strains which were reported to belong to different serotypes also appeared closely related. Thus, only three major groups, clearly distinct from each other, could be formed. Apart from this, a search for the exact cleavage site of the unprocessed polyprotein of IPNV was done since the amplified fragment used for sequencing was localized at the junction between two polypeptides of the virus, pVP2 and NS. No obvious sequence or dipeptide appeared conserved in all birnaviruses.

Amino Acid Sequence↗
PubMed1993

Antigenic characterization of serogroup 'A' of infectious pancreatic necrosis virus with three panels of monoclonal antibodies.

Monoclonal antibodies (MAbs) were produced against three serotypes of infectious pancreatic necrosis virus (IPNV): A1 (LWVRT 60-1, U.S.A.), A2 (d'Honnincthun, France) and A9 (Jasper, Canada). Each panel of MAbs (identified as LW, HF and JA) was analysed by ELISA with the 10 proposed serotypes of IPNV and their specificity defined by immunoprecipitation and Western immunoblotting analysis. A first group of MAbs, directed against the outer capsid protein VP2, reacted with linear or conformational epitopes. A second group of MAbs, directed against the internal protein VP3, reacted with linear epitopes. There was no relationship between the neutralizing property of anti-VP2 MAb and the configuration of the epitope that it recognized. The MAbs were used for antigenic characterization of serogroup A. Each panel of MAbs showed a characteristic pattern of reactivity. The European HF series was predominantly cross-reactive and detected conserved epitopes among the 10 serotypes for both VP2 and VP3. The North American LW and JA series identified a group of conserved epitopes on VP3 and new specific epitopes on VP2 and VP3. The higher variability observed for VP2 in comparison with VP3 is one example of how external pressures may promote natural selection of those epitopes required for virus survival. Our results are consistent with an ancestral relationship of the European to the North American strains, the latter having developed new antigenic determinants upon evolution in their new geographical location.

Animals↗
PubMed1992

Evidence of genomic variations between infectious pancreatic necrosis virus strains determined by restriction fragment profiles.

Infectious pancreatic necrosis virus (IPNV) is the aetiological agent of an important disease in hatchery-reared salmonid fish in North America, Europe and Japan. It belongs to the family Birnaviridae and shows a high degree of antigenic heterogeneity. However, genomic variations between the 10 identified serotypes have not yet been studied. In order to correlate genomic heterogeneity with the different serotypes, oligonucleotides were synthesized according to the published sequence of the Jasper strain (serotype A9). They were used as primers for the amplification of a 359 bp cDNA fragment of the viral genome using the polymerase chain reaction. Fragments amplified from 37 strains were digested with five different restriction enzymes. Restriction fragment profiles obtained an agarose gels showed heterogeneity not only between strains of different serotypes, but also among those belonging to serotype A1. A cluster analysis of the restriction patterns showed that IPNV strains can be divided into three major groups, corresponding approximately to serotypes A1, A2 and A3, and 10 subgroups which do not correlate with the serotyping of the strains.

Animals↗
PubMed1992

Antigenic and genomic differences of two Jasper strains of infectious pancreatic necrosis virus.

Strains of infectious pancreatic necrosis virus (IPNV-Jasper) obtained from two different laboratories were compared serologically with polyclonal and monoclonal antibodies. Nucleotide sequence and restriction endonuclease patterns of 359-bp fragment of genome segment A cDNA were also compared. Substantial differences were found in both analyses that will support the fact that the two Jasper strains are not identical.

Animals↗