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Biomedical subjects

P Bernard

Publications and source records attributed to P Bernard.

At least 163 records · Page 9Linked to original sources
PubMed1998

Factors affecting both peripheral blood progenitor cell mobilization and hematopoietic recovery following autologous blood progenitor cell transplantation in multiple myeloma patients: a monocentric study.

The aim of the study was to analyze the factors influencing peripheral blood progenitor cell (PBPC) collection after high-dose cyclophosphamide (HDCYC) (7 g/m2) and hematopoietic recovery after autologous transplantation of HDCYC-mobilized PBPC (ABPCT) in 116 patients with aggressive multiple myeloma (MM). Following HDCYC 74 patients received hematopoietic growth factors (HGF), either G-CSF (n = 19) or GM-CSF (n = 55). All the patients were subsequently planned to undergo ABPCT. PBPC collection was possible for 106 patients. The most important prognostic factor for collection of more than 25 x 10(4) CFU-GM cells/kg and 2 x 10(6) CD34+ cells/kg was the use of HGF (P = 0.002 and 0.009, respectively). Previous use of an alkylating agent, response to treatment before HDCYC, and interval between diagnosis and HDCYC were also significant factors (P = 0.004, 0.025 and 0.001, respectively). The number of CFU-GM cells infused was the most important parameter for rapid and complete hematological recovery after ABPCT (P < 0.0001). Thus the use of HGF post-HDCYC is the major factor which, associated with reduced time between diagnosis and HDCYC and the use of an alkylating agent, could increase the numbers of hematopoietic progenitors collected, and subsequently improve hematopoietic recovery following ABPCT in MM patients.

Adult↗
PubMed1998

Pyoderma gangrenosum complicating Cogan's syndrome.

Cogan's syndrome is a rare clinical entity defined by the association of a nonsyphilitic interstitial keratitis and vestibuloauditory dysfunction, typically Menière's disease-like; the condition has been reported in association with a variety of cutaneous diseases. We now report a case of pyoderma gangrenosum complicating Cogan's syndrome in a 57-year-old woman, which then healed dramatically, as more interestingly did the associated uveitis with minocycline therapy.

Ataxia↗
PubMed1998

The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index.

OBJECTIVE: To develop a simple prognostic index for anticipating more precisely the early clinical course of primary superficial bladder cancer. PATIENTS AND METHODS: The prognostic value of patient and tumour characteristics was examined in 333 patients with primary Ta or T1 bladder cancer who participated in a multicentre prospective study already completed. Primary tumour multiplicity, a diameter of > 3 cm, stage T1, and grade 2 or 3 were independent predictors of earlier recurrence in a multivariate analysis. A simplified prognostic index consisted of the number of adverse tumour characteristics (ATCs) initially present. RESULTS: After a median follow-up of 35.3 months, the 60 patients free of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and 69%, respectively, and none experienced progression. Recurrence outcomes deteriorated consistently as the number of ATCs increased among the other three groups. In patients with 3-4 ATCs, the 12- and 24-month recurrence-free probability was as low as 30% and 19%, and recurrence and tumour rates were about 2.6 times higher than in patients free of ATCs; 7% of these patients experienced progression within 35 months of follow-up. CONCLUSION: A prognostic index based on the number of ATCs (primary tumour multiplicity, diameter > 3 cm, stage T1, and grade 2 or 3) is a strong indicator of the clinical course of superficial bladder cancer within 3 years of the first endoscopic resection. This proposal is suggested for discussion and for validation in future studies but if confirmed, this simple prognostic index may greatly help to identify indicators for adjuvant intravesical therapy and to determine the optimal periodicity of control cystoscopy regimens.

Adult↗
PubMed1998

Application of Kohonen Neural Networks in classification of biologically active compounds.

Automated data classification is an indispensable tool in Drug Design. It allows to select homogeneous training sets or to distinguish compounds with required biological properties. The Kohonen Neural Networks (KNN) suggest new means for classification of biologically interesting compounds. In this paper, first, capabilities of KNN in data dimensionality reduction are presented as compared with the capabilities of Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). The advantages of KNN become evident with increasing data dimensionality and size of the training set. Then, new methods are suggested to evaluate the quality of KNN models. Finally, a case study on chemical and biological data is presented. The database studied includes more than 2000 organophosphorous potent pesticides. The Kohonen maps were obtained which allow to distinguish compounds with different biological behavior.

Cluster Analysis↗
PubMed1998

Pancreatic trypsinogen I expression during cell growth and differentiation of two human colon carcinoma cells.

Pancreatic trypsin has been found to induce tight junction or dome formation in some colon cancer cell lines (HT-29, Caco-2), and a tumor-associated trypsinogen, trypsinogen type II, has been isolated from another colon cancer cell line (COLO 205). We have tried to determine if trypsinogen is present and how its expression varies during cell culture in HT-29 Glc+/- and Caco-2 cells, which exhibit enterocytic differentiation, and in HT-29 Glc+ cells, which never differentiate. Trypsinogen mRNA presence and expression were demonstrated in these cells by mRNA hybridization, RT-PCR, cytoimmunofluorescence, Western immunoblot analysis, and gel filtration. Trypsinogen was found to be trypsinogen type I and was mainly in zymogen form in culture media. Differentiating cells exhibited variations in trypsinogen I expression, but cells that remained undifferentiated did not. In the differentiated cells, a high and transient peak in trypsinogen I expression was observed during the first steps of differentiation.

Adenocarcinoma↗
PubMed1998

D-dimer strategy in thrombosis exclusion--a gold standard study in 100 patients suspected of deep venous thrombosis or pulmonary embolism: 8 DD methods compared.

DD are now recognized as a valuable tool to screen patients suspected of deep venous thrombosis or pulmonary embolism before carrying out a gold standard radiologic examination. The newest methods available claim to be able to ascertain the absence of thrombosis, but they have yet to prove their efficiency. We compared the performances of 3 reference ELISA methods (D-DI Asserachrom Stago, D-dimer Enzygnost Behring and Dimertest GOLD EIA Agen), 5 recent rapid methods (VIDAS D-Dimer bioMérieux, Instant IA Stago, Simplired Agen, Nycocard D-dimer Nycomed and Accuclot D-Dimer Sigma Diagnostics) and two routine latex methods (Dimertest American Diagnostica and FDP-Slidex bioMérieux) in 100 patients. One of the rapid quantitative methods was demonstrated to have a level of efficiency comparable to that of ELISA methods. Finally, the cost and efficiency of different strategies were evaluated, the association of a routine latex method with the VIDAS D-Dimer bioMérieux being proven to be the most efficient.

Adult↗
PubMed1998

Variable expression of Mn SOD in three different human melanoma cell lines.

In recent studies, decreased expression of Mn SOD, an intramitochondrial enzyme responsible for the dismutation of anion superoxide, has been reported in multiple, malignant cell types, whereas its gene has been proposed as a tumour suppressor gene in melanoma. We studied the expression of Mn SOD both at genetic (DNA, mRNA) and protein levels in three human melanoma cell lines (M3 Da, M4 Be, M1 Do). All cell lines were tumorigenic in a nude mouse model. In these cell lines, Mn SOD was studied at the molecular level using PCR of genomic DNA, and by RT-PCR of total mRNA extracts to detect Mn SOD transcripts. Mn SOD protein expression was studied by indirect immunofluorescence using a monoclonal antibody anti-human Mn SOD (Bender) on suspended cells fixed on slides after cytospin. All three human melanoma cell lines studied contained detectable amounts of DNA and mRNA specific for the Mn SOD gene. In contrast, there was variable expression of Mn SOD at the protein level. As detected by immunofluorescence, Mn SOD protein was expressed in only two cell lines (strongly in M3 Da, weakly in M4 Be) but not in M1 Do. These preliminary, qualitative results demonstrate that the deficit of Mn SOD protein expression is variable depending on the particular melanoma cell line. Further investigations are required in order to evaluate quantitative Mn SOD protein expression and activity as well as the level of functional Mn SOD mRNA and DNA in these or other cell lines.

Animals↗
PubMed1998

p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer.

Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 protein accumulation (P = .0477). Prolonged chemotherapy, however, was associated with little or no change in survival among patients whose tumor expressed those markers. The present study adds support to the hypothesis linking c-erbB-2 and p53 expression to drug resistance.

Adult↗
PubMed1998

[ECG anomalies and axis deviations in heart transplant recipients: MRI studies].

The electrocardiogram is often abnormal after orthotopic cardiac transplantation. This study was conducted in order to evaluate the frequency of these abnormalities in a population of 29 patients transplanted according to the conventional mode or the total mode. We also investigated the correlation between these abnormalities and the presence of left ventricular hypertrophy or deviation of the left ventricular long axis. The left ventricular mass was measured by TM echocardiography. The position of the left ventricular long axis was determined by MR on a ultrarapid sequence. The ECG was normal in 5 patients. The abnormalities revealed in the other 24 patients were: an rSr' or rsr' appearance in V1 with a QRS complex less than 0.12 sec in 11 patients, complete right block in 1 patients, repolarization abnormalities (apart from those associated with branch blocks) in 8 patients, left axis deviation of the QRS in 5 patients, a biphasic P wave in V1 with a Morris index greater than 4 mV.sec in 5 patients, and double atrial activity in 3 patients. These abnormalities were observed regardless of the type of transplantation, with the exception of double atrial activity which was only observed in the group of patients undergoing conventional transplantation. On average, the long axis of the left ventricle was more horizontal and deviated to the left compared to age- and sex-matched controls. All patients with left axis deviation of the QRS had left ventricular hypertrophy versus 13 of the 24 patients without QRS axis deviation and abnormalities of position of the anatomical left ventricular long axis. Our results therefore suggest that the frequent presence of right branch block in heart transplant recipients is due to factors other than the position of the heart in the thorax, for example right ventricular hypertrophy.

Adult↗
PubMed1998

[African tick-bite rickettsiosis: the 1st case of autochthonous infection?].

BACKGROUND: African tick-bite fever is caused by R. africae. All cases reported to date in France have occurred among patients who came from southern Africa, the endemic zone. We report the first case, to our knowledge, of a patient infected in France. CASE REPORT: A 69-year-old white man who had never left France developed fever and 3 "black spots" on the legs with lymphangitis and enlarged nodes. The clinically suspected diagnosis was confirmed by positive serology reactions to R. africae. As cross immunity with R. conorii can occur, the diagnosis was further confirmed by western blot for R. africae and by the persistence of the reaction after adsorption of the R. conorii serum. DISCUSSION: African tick-bite fever was identified as a clinical entity different from Mediterranean spotted fever by Kelly in 1992 who demonstrated the causal role of R. africae. The typical clinical presentation associates fever, several black spots, lymphangitis and multiple node enlargement. The serological diagnosis is difficult owing to cross immunity with R. conorii. Western blot and polymerase chain reaction are required for definitive diagnosis. In our case, the infection was probably due to a R. africae imported into France in the luggage of the patient's daughter who had spent 3 months in Zimbabwe.

Aged↗
PubMed1997

Study of the apoptosis induced in vitro by antitumoral drugs on leukaemic cells.

A flow cytometric method for simultaneous apoptotic cell detection and cell cycle analysis was applied on the U937 cell line. Four antitumoral drugs currently used in the treatment of acute myeloid leukaemia were studied in vitro: DNR, IDR, MITO and Ara-C. Our results show a dissociation between the cytostatic effect (the block in the cell cycle observed for low drug concentrations) and the cytotoxic effect (the induction of apoptosis induced by higher concentrations) for all the tested molecules. Low concentrations of Ara-C induced a block in the S phase while higher concentrations (>10(-7) M) induced apoptosis at the G1-S boundary. Low concentrations of anthracyclines (<40 nM DNR and <20nM IDR) induced a block in G2 without apoptosis. Apoptosis was induced in G1 and/or early S phases by higher concentrations of anthracyclines. The concentration inducing 50% apoptosis (IC50) was found to be, respectively, 200 and 40 nM for DNR and IDR. Analysis of MITO-treated cells showed a parallel increase in the percentages of S phase and apoptotic cells. However, the bivariate analysis showed that apoptosis did occur in a population with G1 DNA content. For two other drugs (CAM and COLC), apoptosis occurred for the same concentrations and in the same phase as the block (in S and G2M, respectively). The IC50 of MITO was found to be 100 nM. Cotreatment of the cells with colchicin and either Ara-C or IDR showed that the passage through mitosis was not necessary for the completion of apoptosis at the G1-S boundary. Short incubations of U937 cells with high concentrations of anthracyclines were found to be efficient in inducing further apoptosis. We conclude that, for all the assayed molecules, the cytotoxic and/or cytostatic effects of the antitumoral drugs tested greatly depend on the concentrations used and that, depending on their in vivo pharmacokinetics, the induction of apoptosis could be an important mechanism of action for some of these drugs.

Acute Disease↗
PubMed1997

In vitro cytotoxic effects of 4,4'-bipyridyl on normal human keratinocytes.

Recent epidemiological studies have brought to light a possible link between premalignant or neoplastic skin lesions (Bowen disease, squamous carcinoma) and occupational exposure to 4,4'-bipyridyl (4,4'B), a precursor in the synthesis of paraquat herbicide. The present study used a serum-free cell culture of normal human keratinocytes (NHK) and two skin-equivalent models to test the effects of exposure to different concentrations of 4,4'B. Cytotoxicity of 4,4'B on NHK was measured by neutral red release assay. Superoxide dismutase (SOD) activity and cell cycle were analyzed in exposed and nonexposed NHK cultures. Histological and immunohistological tests enabled evaluation of differentiation and proliferation effects in reconstructed-skin models. Results showed that significant cytotoxicity occurred after 5 to 11 days' exposure to 4,4'B concentrations of 10(-6)-10(-3) mol/L (IC50 between 10(-3) and 10(-4) mol/L 4,4'B after 11 days). Parallel modifications of SOD activity were recorded. Histological and immunohistological analysis revealed dose-related 4,4'B effects in reconstructed skin models. This involved abnormal terminal differentiation, connected with filaggrin expression, observed in skin models exposed to 10(-7) and 10(-6) mol/L 4,4'B. However, no modification of cell cycle or dysplasia was detected as a result of exposure to 4,4'B. Thus, 4,4'B appears to be cytotoxic for NHK, but as an isolated contaminant, and is unable to induce keratinocyte dysplasia in vitro. These preliminary results do not exclude a cocarcinogenic action of 4,4'B (with UVB for example).

Cell Cycle↗
PubMed1997

Bcr-abl translocation can occur during the induction of multidrug resistance and confers apoptosis resistance on myeloid leukemic cell lines.

Apoptosis was studied in parental and mdr-1 expressing U937, HL60 and K562 myeloid leukemic cell lines using mdr unrelated inducers of apoptosis such as Ara-C, cycloheximide, serum deprivation, ceramide, monensin and UV irradiation. Apoptosis was efficiently induced by all these treatments in U937 and HL60 cells while K562 cells exhibited an apoptosis-resistant phenotype except with UV and monensin. The pattern of apoptosis resistance in mdr-1 expressing U937 (U937-DR) and HL60 (HL60-DR100) was similar to that presented by K562. This apoptosis-resistant phenotype of mdr cells was not overcome by concentrations of verapamil inhibiting the P-gp 170 pump. The acquisition of this phenotype was posterior to the mdr-1 expressing phenotype since a HL60-DR5 variant, selected at the beginning of the induction of resistance, presented a low level of mdr-1 expression without resistance to apoptosis. The variations observed in the Fas (CD95) expression between sensitive and resistant cells were not sufficient to account for apoptosis resistance. However, a high expression in Abl antigen was found in all the apoptosis-resistant cells. RT-PCR and Western blot analysis showed that this increase in Abl antigen content was accompanied by the expression in U937-DR and HL60-DR100 cells of a hybrid bcr/abl mRNA and a 210 kD Bcr/Abl protein which was constitutive in K562. This expression was due to the translocation of abl and the amplification of the bcr-abl translocated gene. These results are in agreement with the role of Bcr/Abl tyrosine protein kinase as an inhibitor of apoptosis independently of the mdr-1 expression. They also suggest that translocation of the abl gene in the bcr region is a highly probable rearrangement in the mdr-1 expressing myeloid cells and that Bcr/Abl tyrosine kinase effect on apoptosis needs the regulation of intracellular pH and is inactive against UV-induced apoptosis.

Journal Article↗