Search PubMed⌕ Search

Biomedical subjects

F Bernard

Publications and source records attributed to F Bernard.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Congenital quadricuspid aortic valves].

BACKGROUND: Quadricuspid aortic valve is an uncommon congenital anomaly. We report a case in a patient hospitalized for heart failure. CASE REPORT: A 62-year old patient with exercise-induced dyspnea was hospitalized for heart failure. Heart auscultation revealed a diastolic aortic murmur attributed to a quadricuspid aortic valve evidenced at echocardiography. DISCUSSION: Quadricuspid aortic valves usually have three cusps of equivalent size and a small fourth cusp between the right coronary cusp and the non-coronary cusp. Aortic regurgitation is usually observed requiring valve replacement in 50% of the cases. The anomaly may be associated with other congenital anomalies of the coronary arteries warranting systematic coronarography prior to valve replacement.

Aortic Valve↗
PubMed1998

Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression.

p120 GTPase-activating protein (p120GAP) is a major negative regulator of p21ras activity in several cell types including T cells. Catalytic activity of this enzyme is regulated in part by its interaction with several associated tyrosine-phosphorylated proteins. Sam68 was initially described as associated with p120GAP. It has been further established that Sam68 is a substrate of src kinases in mitosis and that it is not associated with p120GAP in transformed fibroblasts. We describe herein that Sam68 associates with p120GAP and PLC gamma 1 in human mature T cells and in a T cell line expressing the CD4 molecule HUT78 CD4+. This association is present in nonactivated cells and increases after anti-CD3 activation. It is dependent on CD4 expression and, in part, on the association of CD4 with p56lck, as shown by the strongly decreased association of Sam68 with p120GAP in the CD4- mutants, HUT78 CD4-, and by the reduced association of Sam68 with both p120GAP and p56lck in the HUT78 T cell line expressing a CD4 mutant unable to interact with p56lck, HUT78 C420/22. We propose that recruitment of Sam68, via CD4/p56lck, to the inner face of the plasma membrane may permit, via its docking properties, the correct association of key signaling molecules including PLC gamma 1 and p120GAP. This formation of transduction modules will enable the activation of different signaling cascades including the p21ras pathway and an array of downstream events, ultimately leading to T cell activation.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Ligands of CD4 inhibit the association of phospholipase Cgamma1 with phosphoinositide 3 kinase in T cells: regulation of this association by the phosphoinositide 3 kinase activity.

We have previously shown that CD4 ligands inhibit interleukin-2 (IL-2) production and T cell proliferation in human peripheral CD4+ T lymphocytes, in an MHC-independent way. Two major pathways implicated in T cell activation are inhibited by binding of CD4 ligands to the CD4 molecule, i.e. Ca2+ signaling by phospholipase Cgamma1 (PLCgamma1), and ERK-2 activation, suggesting a p21ras inhibition. We have correlated these inhibitions with the disruption of multifunctional complexes containing PLCgamma1, p120GAP and Sam68, induced by T cell activation. We report here that T cell activation through the TCR/CD3 induces an association of the phosphoinositide 3 kinase (PI3 kinase) with PLCgamma1, both in peripheral CD4+ T lymphocytes and the HUT-78 CD4+ T cell line. PI3 kinase is present in the multifunctional complexes that we have described previously. Preincubation of human peripheral CD4+ T cells and HUT-78 CD4+ T cells with gp160 or a peptide analogue of the HLA class II DR molecule precludes the association of PLCgamma1 with PI3 kinase. We also demonstrate, using two specific inhibitors of PI3 kinase activity (LY294002 and wortmannin), that this activity plays a key role in the association of PLCgamma1 with PI3 kinase. Moreover, we demonstrate the implication of the PI3 kinase activity in the negative signal mediated by HIV gp160 binding to CD4 molecules. We propose that the products of the PI3 kinase are important mediators of the negative signaling induced by the binding of CD4 ligands to the CD4 molecule implicated in the regulation of the formation of multifunctional complexes.

Amino Acid Sequence↗
PubMed1998

The protein tyrosine kinase p60c-Src is not implicated in the pathogenesis of the human autosomal recessive form of osteopetrosis: a study of 13 children.

Osteopetrosis has been described in mice generated by homozygous gene disruption of c-src gene encoding for the p60c-Src protein tyrosine kinase (Src-/- mice). The similarities of bone histologic findings in this murine model to those observed in some patients first seen with autosomal recessive osteopetrosis, "malignant" osteopetrosis, led us to investigate the potential role of p60c-Src in the pathogenesis of malignant osteopetrosis in 13 children. In 4 patients a c-src mutation was ruled out by an intragenic microsatellite segregation study. In the other 9 we analyzed p60c-Src expression and function, as well as c-src sequence. The expression was normal in all of the patients tested. In addition, the tyrosine phosphorylation and kinase activity of p60c-Src were also normal in all of the patients. Moreover, in these patients, sequences of the coding region of c-src were identical to the published sequence of the human c-src complementary DNA. These results exclude a role for c-src in the pathogenesis of human malignant osteopetrosis in the 13 patients analyzed.

Antibodies, Monoclonal↗
PubMed1998

[False aneurysm of the left ventricle. A sometimes late finding].

Left ventricular pseudo-aneurysm is a rare complication of myocardial infarction, usually of the inferior wall. It is generally a sudden event due to rupture of the heart which is contained by the pericardium. The outcome is usually rapidly fatal by secondary rupture or adiastole. The authors report a case of pseudo-aneurysm of the left ventricle measuring 3.5 cm in diameter observed following a small inferior wall myocardial infraction in a diabetic patient with a history of inferior wall myocardial infarction 38 years previously. This case is interesting because of the silent character of the pseudo-aneurysm, very probably complicating the previous infarct.

Aged↗
PubMed1998

[Constrictive pericarditis: an underestimated complication of thoracic injuries].

Constrictive pericarditis is a well defined clinical entity, traditionally secondary to longstanding tuberculosis. Although posttraumatic constrictive pericarditis, due to haemopericardium, is well known during the postoperative period following cardiac surgery, it is underestimated in closed chest trauma. A new case of constrictive pericarditis is reported, due to neglected chest trauma. The discussion emphasizes the need for early diagnosis and surgical treatment, which determine the general prognosis of pericardial constriction. This implies systematic investigation of all cases of chest trauma, even minor, by transthoracic, or preferable, transoesophageal echocardiography, looking for haemopericardium.

Echocardiography, Transesophageal↗
PubMed1998

[Coronary vessel ectasia: coronary artery disease with a high thromboembolic risk].

Coronary dystrophy is characterized by the presence of successively stenotic and ectatic or even aneurysmal zones in the coronary network. The authors report a new case of coronary ectatic dystrophy presenting in with myocardial infarction. They review the literature and suggest the various aetiologies, the main one being atherosclerosis. The management of this particular form of atherosclerosis is dominated by the thromboembolic risk related to these aneurysmal zones responsible for myocardial infarction, justifying long-term anticoagulant therapy.

Adult↗
PubMed1997

Abnormal CD40-mediated activation pathway in B lymphocytes from patients with hyper-IgM syndrome and normal CD40 ligand expression.

The CD40-mediated activation pathway of B cells from 10 patients with hyper-IgM syndrome and normal expression of CD40 ligand was studied. In all 10 cases, B cells were found to be defective for IgG, IgA, and IgE production after stimulation by anti-CD40 mAbs and cytokines. In the patients tested, neither B cell proliferation (n = 6) nor CD23 molecule expression (n = 5) were observed in cultures stimulated with anti-CD40 mAb. These results point to an intrinsic B cell deficiency and a defect in the CD40-triggered B cell activation pathway; this conclusion was supported by a lack of detectable germinal centers in the spleen of two patients. CD40-triggered activation events, i.e., phosphatidylinositol 3 (PI3) kinase activation and induction of transcription factors NF-kappaB and AP-1, were next analyzed in B cell lines derived from five patients. Three distinct patterns were observed: an absence of detectable abnormalities (n = 1), defective PI3 kinase activation with normal induction of NF-kappaB and AP-1 (n = 3), and defects in both PI3 kinase activation and induction of NF-kappaB and AP-1 (n = 1). In three B cell lines, each exhibiting one of the CD40-mediated activation patterns, sequences of CD40 and CD40 binding protein coding regions were normal. The coding region of TNF receptor-associated factor 2 (TRAF2), which is known to interact with CD40 for NF-kappaB induction, was also found to be normal in B cell lines deficient in NF-kappaB induction. Altogether, these results suggest that CD40 ligand-positive hyper-IgM syndrome could be genetically heterogeneous, although phenotypic variability is not excluded, and that an early defect in the CD40-triggered activation cascade can account for defective Ig class switching in some patients with CD40 ligand-positive hyper-IgM syndrome.

Adolescent↗
PubMed1997

CD4 ligands inhibit the formation of multifunctional transduction complexes involved in T cell activation.

Ligands binding to the CD4 molecule can inhibit TCR-mediated T cell activation. We have previously reported that transcription factors regulating the expression of the IL-2 gene, NF-AT, NF-kappaB, and AP-1, are targets of this inhibitory effect in an in vitro model using peripheral human CD4+ T cells activated by a CD3 mAb. Two T cell activation pathways involved in the regulation of these transcription factors, calcium flux and the p21ras pathway, were investigated as potential targets. Binding of HIV envelope glycoprotein gp160/gp120 or a CD4 mAb to the CD4+ T cells, prior to TCR/CD3 activation, inhibited the intracellular calcium elevation. This event strongly suggested an inhibition of PLCgamma1 activity. Tyrosine phosphorylation of PLCgamma1, induced by CD3 activation, was not affected, but its association with tyrosine-phosphorylated proteins, including a 62-kDa protein, was disrupted. This PLCgamma1-associated p62 was found to be immunoreactive to p62-Sam68 Abs. The activation-induced phosphorylation of two p21ras effectors, Raf-1 and Erk2, was inhibited by the CD4 ligands, indirectly pointing to inhibition of the p21ras activation pathway. In addition, we demonstrate that TCR activation of normal CD4+ T cells induced the formation of p120GAP and PLCgamma1-containing complexes. These complexes also contain other unidentified proteins. CD4 ligand binding induced a defective formation of these transduction complexes. This may result in inefficient signaling, partially accounting for the inhibitory effects of the CD4 ligands on both p21ras and calcium-activation pathways.

Antibodies, Monoclonal↗
PubMed1997

Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core antibody and HBV DNA in monitoring the response to treatment in patients with chronic hepatitis B.

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-alpha (IFN-alpha). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.

Alanine Transaminase↗
PubMed1997

GLUT2 and hexokinase control proximodistal gradient of intestinal glucose metabolism in the newborn pig.

We have reported previously that a high glycolytic capacity develops soon after birth in enterocytes isolated from suckling newborn pigs. In the present work, we investigated whether such metabolic changes could affect intestinal glucose utilization in vivo and examined possible variations in glucose metabolism along the small intestine. Glucose utilization by individual tissues was assessed using the 2-deoxyglucose technique. The overall glucose utilization rate was doubled in suckling vs. fasting 2-day-old pigs because of significantly higher rates in all tissues studied, except for the brain. In parallel, enterocytes were isolated from the proximal, medium, or distal jejunoileum of newborn vs. 2-day-old pigs and assessed for their capacity to utilize, transport, and phosphorylate glucose. Intestinal glucose consumption accounted for approximately 15% of glucose turnover rate in suckling vs. 8% in fasting pigs. Moreover, there was a proximal-to-distal gradient of glucose utilization in the intestinal mucosa of suckling pigs. Such a gradient was also evidenced on isolated enterocytes. The stimulation of both hexokinase activity (HK2 isoform) and basolateral glucose transporter (GLUT2), as observed in the proximal jejunum, could account for such a site-specific effect of suckling.

Animals↗
PubMed1997

[Myocardial infarction caused by exertion].

Myocardial infarction is the main cause of sudden death during physical exercise, particularly in subjects over 40 and may even occur in high-performance young athletes. Sports and physical activity have a beneficial effect in preventing cardiovascular diseases, but certain rules of prudence must be followed to avoid the risk of a severe coronary event. Myocardial infarction always occurs in particularly susceptible subjects with several risk factors, predominantly smoking, hypercholesterolemia, family history of atherosclerosis. Dietary factors, either before, during or after the exercise, are always found. Distribution of coronary lesions differs with age. Before 40 years, the coronary network is normal in 40% of the cases. The infarction is partially explained by platelet hyperaggregahility and coronary spasms at exercise or in the post-exercise period.

Age Factors↗
PubMed1997

PP60c-src expression in osteoclasts from osteopetrotic children and in giant tumor cells.

Malignant infantile osteopetrosis is a severe congenital disease characterized by impaired osteoclast activity. Among the multiple factors that influence bone resorption, the c-src protooncogene product pp60c-src plays an essential role, since mice which lack pp60c-src develop osteopetrosis. To gain insight into the possible role of pp60c-csrc in the pathogenesis of infantile osteopetrosis, we examined the osteoclasts of three children displaying the typical features of the disease, aged respectively one, four and seven months. pp60c-csrc expression and localization, together with the expression of a 80/85-kilodalton pp60c-src substrate, cortactin, were examined by immunoelectron microscopy. Osteoclasts from two giant cell tumors were used as controls. Bone and tumor samples were fixed in 4% paraformaldehyde, included in LR-White resin at -30 degrees C and the sections processed with mAb 327 or mAb anti p80/85 by an immunogold technique. pp60c-src was expressed in the cytoplasm, in nuclear membranes and in nuclei of the osteoclasts of the three osteopetrotic children. The subcellular localization of the kinase was not different from the localization in giant tumor cells. In both cases cortactin was abundant. In conclusion, in three children with malignant osteopetrosis, pp60c-src expression in osteoclasts does not appear to be involved in the pathogenesis of the disease. The presence of this protein, however, does not necessarily reflect normal c-src tyrosine kinase activity, nor normal c-src-dependent intracellular signaling pathways. Moreover the presence of the protein in nuclear membranes, and especially around nuclear pores supports the hypothesis that in osteoclasts, c-src may participate in the regulation of RNA processing.

Adolescent↗
PubMed1996

Immunohistochemical study on the reactivity of workshop monoclonal antibodies with sheep lymph nodes.

Of the 302 monoclonal antibodies submitted to the Third Workshop on Ruminant Leukocyte Antigens, 167 have been tested for their reactivity on sheep lymph node sections, according to the APAAP immunohistochemical technique. Of the 57 monoclonal antibodies able to react on ovine tissue sections, only 37 induced a clear and well-contrasted staining. The more striking results are presented in this paper.

Animals↗
PubMed1996

Flow cytometric analysis of the reactivity of workshop monoclonal antibodies on sheep lymph node cells, after infection with Salmonella abortusovis.

Of the 302 monoclonal antibodies included in the Third Workshop on Ruminant Leukocyte Antigens, 167 have been tested for their reactivity on uninfected and Salmonella-infected sheep lymph node leukocytes using FACS analysis. Only 47 of them showed specificities which could be related to those of some control monoclonal antibodies, such as the anti-CD5, anti-Ig light chain and anti-MHC Class II monoclonal antibodies.

Animals↗
PubMed1995

An oligomer of the major outer membrane protein of Chlamydia psittaci is recognized by monoclonal antibodies which protect mice from abortion.

Monoclonal antibodies (MAbs) were generated against an ovine abortive strain of Chlamydia psittaci. A plaque reduction assay was used to select 19 neutralizing antibodies which appeared to be heterogeneous in isotype, specificity, and recognized proteins. Different neutralizing MAbs were tested for their protective abilities against abortion in a pregnant-mouse model. All of the protective MAbs selected had the same isotype, were serotype 1 specific, and recognized a protein of about 110 kDa by immunoblotting. The recognized epitopes were resistant to sodium dodecyl sulfate and reducing agents, but all of them were heat sensitive. The protein was able to form disulfide-linked polymers. Immunological cross-reaction studies with rabbit sera showed a link between the 110-kDa protein and the major outer membrane protein (MOMP). The 110-kDa protein was purified by immunoaffinity and shown to be dissociated after heating into MOMP by silver staining and immunoblotting. These results show homogeneity among protective MAbs directed to heat-sensitive epitopes located on an oligomer of the MOMP of C. psittaci.

Abortion, Veterinary↗