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Biomedical subjects

P Bernard

Publications and source records attributed to P Bernard.

At least 127 records · Page 7Linked to original sources
PubMed1999

Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases.

This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node-positive (NPBC) and node-negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow-up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin-3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer.

Adenocarcinoma↗
PubMed1999

Expression and activation of pro-gelatinase A by human melanoma cell lines with different tumorigenic potential.

The production of various proteolytic enzymes by tumor cells facilitate the invasion of solid tumors into surrounding tissues. We examined three cell lines (M1Dor, M4Be and M3Da) derived from malignant melanoma which exhibited different abilities to grow in nude mice following subcutaneous grafting. By in vitro invasion assay using Boyden-chambers technique, we found that none of those cell lines were able to invade the Matrigel. Several studies have substantiated the role of matrix metalloproteinases (MMP), mainly gelatinases MMP-9 and MMP-2, in melanoma cell invasion. Each cell line constitutively produced MMP-2 (but not MMP-9) in its latent form only, with stronger production for the most tumorigenic cell line in vivo (M3Da). Integrity of the MMP-2 activation process was studied since MMP-2 was also recovered as zymogen at the cell plasma membrane. All cell lines secreted TIMP-1 and TIMP-2 in a constitutive manner and again, but TIMP-2 production as well as MT1-MMP expression were found inversely related to their tumorigenic potential. Plating cells onto type I or type IV collagen did not trigger pro-MMP-2 activation; on the contrary, conversion of pro-MMP-2 to its active form could be evidenced when melanoma cell lines were seeded in a three dimensional type I collagen lattice.

Blotting, Northern↗
PubMed1999

Automated docking of 82 N-benzylpiperidine derivatives to mouse acetylcholinesterase and comparative molecular field analysis with 'natural' alignment.

Automated docking and three-dimensional Quantitative Structure-Activity Relationship studies (3D QSAR) were performed for a series of 82 reversible, competitive and selective acetylcholinesterase (AChE) inhibitors. The suggested automated docking technique, making use of constraints taken from experimental crystallographic data, allowed to dock all the 82 substituted N-benzylpiperidines to the crystal structure of mouse AChE, because of short computational times. A 3D QSAR model was then established using the CoMFA method. In contrast to conventional CoMFA studies, the compounds were not fitted to a reference molecule but taken in their 'natural' alignment obtained by the docking study. The established and validated CoMFA model was then applied to another series of 29 N-benzylpiperidine derivatives whose AChE inhibitory activity data were measured under different experimental conditions. A good correlation between predicted and experimental activity data shows that the model can be extended to AChE inhibitory activity data measured on another acetylcholinesterase and/or at different incubation times and pH level.

Acetylcholinesterase↗
PubMed1999

Autologous stem cell transplantation in chronic myeloid leukemia: a single center experience.

Between 1980 and 1996, we transplanted 72 patients with CML using blood stem cells collected at diagnosis before treatment and without any mobilization. The median age of patients at diagnosis was 47.5 years (range 20.5-59.5). The median numbers of nucleated cells and CFU-GM transplanted were 10 x 10(8)/kg and 97 x 10(4)/kg, respectively. The median duration to reach more than 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets was 12 (range 5-19) and 11 days (range 0-79), respectively. Twenty patients (group I) were transplanted in chronic phase either for resistance to IFN (14 patients) (group IA) or because the Sokal index was more than 1.2 (six patients) (group IB). All those patients had preparative regimen with busulfan (4 mg/kg/day x 4) and melphalan (140 mg/m2). They were treated with recombinant alpha-interferon (IFN) after transplant. The cumulative incidence of major cytogenetic response (MCR) at 12 months was 25 +/- 21% (95% CI), the 5-year survival was 75 +/- 42% (95% CI). These results (observed in patients with bad prognosis factors) are similar to those usually observed in CML patients treated by IFN, whatever the Sokal risk. Thus autologous transplantation is able to reproduce for poor prognosis patients the results observed in standard risk patients treated with IFN. This suggests that it could prolong survival. Fifty-two other patients (group II) were transplanted for CML in transformation (accelerated phase = 32; blast crisis = 20) after a preparative regimen containing either total body irradiation (TBI) or busulfan. The median survival was short (10.4 months) and only 21 patients survived more than 1 year. The survival was longer for patients transplanted in accelerated phase (vs blast crisis), those who were due to receive a double transplant (vs single) (34 patients), those who were treated with IFN after transplant (vs hydroxyurea) and for the patients who obtained a complete hematologic response.

Adult↗
PubMed1999

Responses of total and free insulin-like growth factor-I and insulin-like growth factor binding protein-3 after resistance exercise and training in elderly subjects.

To investigate the effects of an acute bout of exercise on total and free insulin-like growth factor-I and insulin-like growth factor binding protein-3 plasma concentrations, 32 healthy elderly subjects (67-80 years, 16 men) performed a strength test, which consisted of two sets of 12 repetitions at 12-repetition maximum and four sets of 5 repetitions at 5-repetition maximum for horizontal leg press, seated chest press, and bilateral leg extension movements. Ten out of the 32 subjects served as time controls. Blood samples were drawn prior (08.30 h), immediately (10.30 h), and 6 h (16.30 hours) after the strength test in exercising and resting subjects. The 32 subjects were then randomly assigned to habitual physical activity or to an 8-week strength training program. After 8 weeks, both sedentary and trained groups underwent blood samplings under the above-mentioned conditions. The exercising group showed increased total and free insulin-like growth factor-I concentrations immediately (+17.7 and +93.8%, respectively), and 6 h (+7.5 and +31.2%, respectively) after the test, whereas no significant changes in insulin-like growth factor binding protein-3 concentrations were observed in either exercising or resting control groups. Strength training induced no significant changes in baseline insulin-like growth factor-I and insulin-like growth factor binding protein-3 concentrations. Trained and sedentary groups showed similar hormonal response pattern to the strength test, which consisted of increased total and free insulin-like growth factor-I concentrations. The data indicated that strength exercise can induce an early and sustained insulin-like growth factor-I release, in elderly subjects, regardless of their training status.

Aged↗
PubMed1999

Neuronal correlates of vestibulo-ocular reflex adaptation in the alert guinea-pig.

The spiking behaviour of 66 second-order vestibular neurons was studied in alert, chronically prepared guinea-pigs during the horizontal vestibulo-ocular reflex (VOR). Among the 66 studied neurons, seven were held long enough (> 1 h) to compare their spiking behaviour before and after a training procedure inducing a decrease in the gain of the VOR. When tested in darkness following adaptation, five of them showed a significant decrease of their sensitivity to head rotation. However, the resting discharge of these five neurons remained unchanged. This suggests that VOR adaptation is mediated not only by changes in synaptic efficacities but also by modifications in the spike generator which transforms synaptic inputs into a pattern of action potentials.

Action Potentials↗
PubMed1999

Automated reticulocyte counting and immature reticulocyte fraction measurement. Comparison of ABX PENTRA 120 Retic, Sysmex R-2000, flow cytometry, and manual counts.

We evaluated reticulocyte counting and measurement of immature reticulocyte fraction (IRF) with the ABX PENTRA 120 Retic blood analyzer on 300 blood samples. Reticulocyte counts were compared with those obtained by visual counting of 2,000 RBCs, by the TOA (Kobe, Japan) Sysmex R-2000 and a flow cytometry method. The parameters analyzed were the percentages of reticulocytes on all analyzers and the IRF with different modalities. The Retic Count kit (Becton Dickinson, San Jose, CA) was used with the Coulter (Hialech, FL) XL, and a mean channel of fluorescence (MCF) was calculated to fit the reticulocyte maturation. Reticulocyte counting with the ABX (Montpellier, France) PENTRA 120 Retic showed excellent precision and linearity with no significant carryover. Reticulocyte counts were stable after blood storage for 72 hours at 4 degrees C but not at room temperature (RT). IRF parameters values were stable for only 8 hours at 4 degrees C and 6 hours at RT. Comparisons of the methods showed good intraclass correlation (RI) for reticulocyte percentages between ABX PENTRA 120 Retic and Sysmex R-2000, ABX PENTRA 120 Retic and flow cytometry, Sysmex R-2000 and flow cytometry, and ABX PENTRA 120 Retic and manual counting. IRF values were correlated between fluorescence rates and RNA content, but in each case, low RI values were found, showing that Sysmex and ABX IRF values were not concordant. We obtained a significant correlation between mean fluorescence index and the MCF measured by flow cytometry, but the 2 methods were not concordant using the RI. The ABX PENTRA 120 Retic is a good instrument for analyzing reticulocyte count and percentage and allows a good analysis of IRF with several modalities.

Acute Disease↗
PubMed1999

Activation of the mouse TATA-less and human TATA-containing UDP-glucuronosyltransferase 1A1 promoters by hepatocyte nuclear factor 1.

UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) catalyzes the glucuronidation of bilirubin in liver. Among all UGT isoforms identified to date, it is the only relevant bilirubin-glucuronidating enzyme in human. Because glucuronoconjugation is the major route of bilirubin elimination, any genetic alteration that affects bilirubin glucuronosyltransferase activity may result in a more or less severe hyperbilirubinemia. In this study, we report the cloning and characterization of the transcriptional regulation of the mouse UGT1A1 gene. Primary-structure analysis of the mouse Thymidine Adevice promoter revealed marked differences with its human homolog. First, the mouse promoter lacks the highly polymorphic thymidine/adenine repeat occurring in the human promoter, which has been associated with some forms of hyperbilirubinemia. Second, an L1 transposon element, which is absent in the human promoter, is found 480 bp upstream of the transcription start site in mouse. Using the electromobility shift and DNase I footprinting experiments, we have identified a hepatocyte nuclear factor 1-binding site in the mouse UGT1A1 promoter that confers responsiveness to both factors HNF1alpha and HNF1beta in HEK293 cells. Furthermore, we show that this element, which is conserved in the human promoter, also confers strong HNF1 responsiveness to the human UGT1A1 gene. Together, these results provide evidence for a major regulatory function of this liver-enriched transcription factor in UGT1A1 activity in both rodents and human.

Animals↗
PubMed1999

Defects in components of the proteasome enhance transcriptional silencing at fission yeast centromeres and impair chromosome segregation.

Fission yeast centromeres are transcriptionally silent and form a heterochromatin-like structure essential for normal centromere function; this appears analogous to heterochromatin and position effect variegation in other eukaryotes. Conditional mutations in three genes designated cep (centromere enhancer of position effect) were found to enhance transcriptional silencing within centromeres. Cloning of the cep1(+) and cep2(+) genes by functional complementation revealed that they are identical to the previously described genes pad1(+) and mts2(+), respectively, which both encode subunits of the proteasome 19S cap. Like Mts2 and Mts4, epitope-tagged Cep1/Pad1 localizes to or near the nuclear envelope throughout the cell cycle. The cep mutants display a range of phenotypes depending on the temperature. Silencing within the central domain of centromeres is increased at 36 degrees C. This suggests that the proteasome is involved in regulating silencing and thus centromeric chromatin architecture, possibly by lowering the level of some chromatin-associated protein by ubiquitin-dependent degradation. This is the first report of defective proteasome function affecting heterochromatin-mediated transcriptional silencing. At 36 and 32 degrees C, the cep mutants lose chromosomes at an elevated rate, and at 18 degrees C, the mutants are cryosensitive for growth. Cytological analysis at 18 degrees C revealed a defect in sister chromatid separation while other mitotic events occurred normally, indicating that cep mutations might interfere specifically with the degradation of inhibitor(s) of sister chromatid separation. These observations suggest that 19S subunits confer a level of substrate specificity on the proteasome and raise the possibility of a link between components involved in centromere architecture and sister chromatid cohesion.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1999

Anti-inflammatory drugs and variceal bleeding: a case-control study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. AIMS: To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. PATIENTS/METHODS: A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. RESULTS: Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2. 9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. CONCLUSIONS: Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.

Adult↗
PubMed1999

Expression of REG protein during cell growth and differentiation of two human colon carcinoma cell lines.

We localized REG protein in Paneth cells and nonmature columnar cells of the human small intestinal crypts and speculated that this protein was associated with growth and/or differentiation. The aim of this study was to determine whether REG protein is present in two human colon cancer cell lines that exhibit enterocytic differentiation after confluence and to investigate changes in the level of its expression during growth and differentiation. Results were compared to those obtained on cells that remain undifferentiated. Western immunoblotting and immunofluorescence demonstrated the presence of REG protein in the three cell lines. With the antisera against human REG protein, the staining was diffusely spread throughout the cytoplasm at Day 2, and after Days 3-4 it appeared to have migrated to cell boundaries. After confluence, we observed only a punctate staining array along cell boundaries, which disappeared at Day 15. REG mRNA expression was demonstrated by RTPCR and REG mRNA hybridization until Day 13, but not after, in the three cell types. REG protein may be involved in cellular junctions. Its presence appears to be associated with the cell growth period and the protein must be downregulated when growth is achieved and differentiation is induced.

Blotting, Western↗
PubMed1999

[Secondary longitudinal melanonychia secondary to onychophagia].

BACKGROUND: Melanonychia of the toenails sometimes results from repeated trauma. This etiology is rarely put forward in lesions affecting the fingernails. CASE REPORT: A 44-year-old woman developed melanonychia affecting 9 fingernails. Genetic predisposition and drug, hormonal or infectious causes were ruled out and we postulated that the lesions were induced by nail biting. DISCUSSION: Nail biting is known to lead to several types of lesions, including melanonychia. The lesions may sometimes disappear several months after stopping this habit.

Adult↗
PubMed1999

Tympanic membrane patching with bandage contact lens after removal of ventilation T tubes.

OBJECTIVE: Early closure of the tympanic membrane, after removal of longstanding ventilation T tubes (VTs), is a desirable outcome. A prospective randomized control study was undertaken to determine if spontaneous healing of the tympanic membrane is promoted with a bandage contact lens (BCL). METHOD: Thirty-nine paediatric patients, who required removal of VTs under general anaesthesia, were selected. After removal of the ventilation tubes, one tympanic membrane was randomly selected for patching with a BCL, while the other underwent conservative management. Follow-up examination was performed at 2 weeks. Remaining perforations of the tympanic membranes were noted. The mean length of time VTs were present was 35.7 months. RESULTS: Chi-square analysis reveals that a significantly greater proportion of tympanic membranes patched with a BCL were healed at 2 weeks (p < .005). CONCLUSIONS: Thus, promotion of spontaneous healing with BCL may allow for decreased risk of infection, improved hearing, and earlier avoidance of precautions necessary for perforated tympanic membranes. Also, it is possible that promoting spontaneous healing at the early phase may decrease the number of persistent tympanic membrane perforations after VT removal.

Adult↗
PubMed1999

[Tolerance and feasibility of adjuvant treatment of stage II malignant melanoma with high-dose interferon-alpha].

BACKGROUND: The use of high-dose interferon alpha as adjuvant therapy has been shown for the first time to improve recurrence-free and overall survival in stage II malignant melanoma. The aim of our work was to evaluate the toxicity of this therapeutic scheme during a 1-year period in 13 patients with malignant melanoma. PATIENTS AND METHODS: Thirteen patients, mean age 56 years, with stage II melanoma were included. Interferon alpha was administered at the dose of 20 MU per m2 body surface area five days per week for four weeks during the induction phase and at the dose of 10 MU subcutaneously three times a week for 48 weeks in the maintenance phase. Patients underwent clinical assessment daily and had blood tests twice a week during the induction phase. Weekly blood tests and monthly examinations were then performed during the maintenance phase. Clinical and biological toxicity was evaluated in accordance with the WHO scores. Grade 3 toxicity led to a 30 p. 100 dose reduction and treatment was interrupted in case of grade 4 toxicity. RESULTS: A flu-like syndrome (grade 1-2) and digestive disorders, nausea, anorexia related to dysgeusia or dry mouth were observed in most of the patients during the induction phase and persisted in 30% of the patients during the maintenance phase. Six patients developed a state of depression (grade 2-3) which persisted during the maintenance phase, inciting us to prescribe an antidepressor regimen for all our patients. One patient developed major reversible alopecia at dose reduction. Nine patients had grade 1 or grade 2 neutropenia and four had grade 3 neutropenia. Seven patients developed grade 1-2 thrombocytopenia, six had elevated transaminase levels (grade 1-2) and two moderately elevated CPK. CONCLUSION: At the end of the induction phase of interferon alpha therapy in 13 patients with malignant melanoma, 8/13 had received 100 p. 100 of the theoretical dose and 11/13 had received 80 p. 100. At the end of the treatment protocol, 5/10 patients had received 100 p. 100 of the theoretical dose and 8/10 more than 80 p. 100. The proposed protocol appears to be feasible without major risk. Rigorous clinical and biological surveillance is mandatory.

Adult↗
PubMed1999

[Normolipemic plane xanthomas and non-Hodgkins malignant lymphomas].

INTRODUCTION: The association between diffuse normolipemic plane xanthomatosis and monoclonal dysglobulinemia is well known. The presence of cutaneous xanthomas with normal serum lipid levels is due to the antibetalipoproteic activity of the monoclonal immunoglobulin. METHODS: A 51-year-old female patient had generalized polyadenopathy and diffuse normolipemic plane xanthomatosis of 3 years duration. The clinical status of the patient was fluctuating. Lipids levels were in the normal range. Weight loss and new nodal enlargements revealed high-grade malignant non-Hodgkin's lymphoma. CONCLUSION: This case illustrates the development of diffuse normolipemic plane xanthomatosis in association with dysglobulinemia revealing non Hodgkin's lymphoma. The association has not been reported earlier in the literature.

Biopsy↗