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Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 73 records · Page 4Linked to original sources
PubMed2001

Proteomics as the tool to search for lung disease markers in bronchoalveolar lavage.

Most lung disorders are known to be associated to considerable modifications of surfactant composition. Numerous of these abnormalities have been exploited in the past to diagnose lung diseases, allowing proper treatment and follow-up. Diagnosis was then based on phospholipid content, surface tension and cytological features of the epithelial lining fluid (ELF), sampled by bronchoalveolar lavage (BAL) during fiberoscopic bronchoscopy. Today, it appears that the protein content of ELF displays a remarkably high complexity, not only due to the wide variety of the proteins it contains but also because of the great diversity of their cellular origins. The significance of the use of proteome analysis of BAL fluid for the search for new lung disease marker proteins and for their simultaneous display and analysis in patients suffering from lung disorders has been examined.

Animals↗
PubMed2001

Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects.

The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase micro-1 (GSTM1) in the responsiveness to O(3)-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O(3) varying from 32 to 103 ppb. Before and after rides, each subject performed spirometric tests and provided a blood sample for the measurement of the Clara cell protein CC16. NQO1 and GSTM1 polymorphisms were characterized by polymerase chain reaction- based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of peripheral leukocytes. Rides at O(3) > 80 ppb resulted in significant decrements of pulmonary function tests and increased levels of serum CC16, consistent with mild impairment in respiratory function and increased lung epithelial permeability, respectively. Whereas NQO1wt and GSTM1null subjects showed both functional changes and increased serum CC16 after acute O(3) exposure, people with other haplotypes showed a rise in serum CC16 but no changes in lung function tests. In NQO1wt and GSTM1null subjects, partial correlation analysis showed that functional decrements and increased serum CC16 are closely associated with each other and with O(3) levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O(3) and hydroquinones would be consistent with the greater increase in 8-OHdG after O(3) exposure in this "susceptible" group.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis.

To test the hypothesis that sarcoidosis is associated with an intravascular leakage of lung epithelium secretory proteins, the occurrence and determinants in serum of sarcoid patients of CC16, a small size and readily diffusible lung-specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated. CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients with established sarcoidosis and of 117 healthy subjects matched for age, sex and smoking status. Stepwise regression analysis was used to identify extrapulmonary variables of CC16 changes in serum. These changes were then compared with biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as well as with the number of CC16 immunostaining cells on bronchial or pulmonary biopsy samples. CC16 concentration in serum of sarcoid patients was significantly increased, compared to their matched controls (25.9 +/- 16.2 versus 13.9 +/- 5.2 microg x L(-1)). In nonsmoking patients without significant renal impairment, CC16 in serum increased with the severity of the chest radiograph and computed tomography changes, and was on average 50-100% higher when parenchymal involvement was present. Sarcoid patients had, however, normal levels of CC16 in BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples, suggesting that an increased secretion of CC16 in the sarcoid lung is very unlikely, and that the elevation of CC16 in sarcoidosis results from an increased intravascular leakage of the protein across the air-blood barrier. The present study suggests that CC16 in serum might provide a useful tool to noninvasively evaluate the damage and increased permeability to proteins of the air-blood barrier associated with sarcoidosis.

Adult↗
PubMed2001

Maternal tobacco smoking and lung epithelium-specific proteins in amniotic fluid.

The bronchiolar 16 kD Clara cell secretory protein (CC16) and the alveolar surfactant-associated protein A (SP-A) are secreted in the amniotic fluid (AF), where they reflect the growth and the maturity of the fetal lung. To evaluate the possible effects of in utero tobacco smoke exposure upon infant bronchoalveolar epithelium function and maturity, CC16 and SP-A levels were determined in AF obtained at term (36-41 wk) from 28 nonsmoking, 18 smoke-exposed, and 28 smoking mothers with uncomplicated pregnancies. Tobacco smoke exposure was assessed by questionnaire and the assay in AF and maternal urine of cotinine, a stable nicotine metabolite. The specificity of the changes of CC16 and SP-A concentrations in AF was assessed by comparison with nonpulmonary proteins of high- (albumin and transferrin) or low-molecular weight (beta2-microglobulin, retinol binding protein, cystatin-C). Pulmonary and nonpulmonary AF proteins were also compared by two-dimensional gel electrophoresis between smoking and nonsmoking mothers. The levels of CC16 and SP-A as well as low- and high-molecular-weight proteins were not significantly different between the three smoking categories. The protein pattern of AF, established by two-dimensional gel electrophoresis, did not reveal any quantitative or qualitative difference between nonsmoking (n = 10), smoke-exposed (n = 5), and smoking mothers (n = 5). By multiple regression analysis of possible determinants, tobacco smoke did not emerge as a significant predictor of CC16 and SP-A concentrations in AF. SP-A level was dependent only on gestational age at birth (r2 = 0.1, p = 0.001), whereas CC16 correlated only with the levels of low-molecular weight proteins (r2 = 0.2, p = 0.0001). The latter correlation suggests that CC16 enters AF not only as a result of its secretion at the surface of the respiratory tract but also partly following its elimination by the fetal kidney. This study suggests that maternal smoking during pregnancy is not associated with alterations of the secretory functions of the epithelium of the distal airways and the alveoli at term.

Adolescent↗
PubMed2001

Influence of the critical EEG pattern on blood flow variations measured by single photon computed emission tomography.

Anatomo-electro-clinical correlation's using stereo-electro-encephalography (SEEG) or electro-cortico-graphy (EcoG) are the gold standard for delineating the epileptic zone (EZ) in patients with partial epilepsy. These two techniques reflect the temporal and spatial dimensions of the epileptic fit. More recently, ictal Single Photon Computed Tomography (SPECT) compared with interictal SPECT allows anatomo-clinical correlations. SPECT reflects variations of the regional cerebral blood flow (rCBF) during the seizure. These variations of the rCBF are linked with the electrical activity but the relations between electrical activity and rCBF have not been well studied and it is still difficult to compare ictal/interictal SPECT with the SEEG and EcoG data to delineate the EZ. From the few published studies, we know that, if the injection of the SPECT tracer is performed at the onset of the seizure, while the fast ictal discharge is still going on, we shall observe a local hyperperfusion in the region where the discharge started and in the region where it propagated secondarily. If the tracer injection is performed late during the seizure, or after the end of it, we shall observe a local hypoperfusion in these regions, this has also a good localizing value. Time of injection must be known, as it represents a key issue for SPECT interpretation.

Journal Article↗
PubMed2000

Astrocytic alterations induced by HTLV type 1-infected T lymphocytes: a role for Tax-1 and tumor necrosis factor alpha.

In the neurological disease associated with HTLV-1 infected T lymphocytes infiltrated within the CNS are suspected of playing a prominent role in pathogenesis via inflammatory cytokines and the viral protein Tax-1. We hypothesized that T lymphocytes initiate functional perturbation in astrocytes, resulting in neuronal alteration as glial cells have a crucial role in CNS homeostasis. In particular, astrocytes manage the steady state level of glutamate and continuously provide metabolite precursors to neurons and oligodendrocytes. Using a model system of HTLV-1-infected T cells-astrocytes interaction, we show that after contact with T cells, astrocyte acquire a phenotype typical of gliosis: secretion of proinflammatory cytokines (TNF-alpha, IL-1alpha, IL-6) and matrix metalloproteinases (MMP-9, MMP-3). The concomitant increase in the expression of MMPs and of their endogenous inhibitors (TIMP-1 and TIMP-3) suggests a perturbation in MMP/TIMP balance. This may alter the extracellular matrix and, in turn, the cell environment. At a functional level, glutamate transport and catabolism are impaired in astrocytes. A decrease in glutamate uptake is associated with downregulated expression of glutamate transporters GLAST and GLT1. The expression of astrocytic enzyme of glutamate metabolism is modified with up-regulation of glutamine synthetase and down-regulation of glutamate dehydrogenase. The involvement of Tax-1 in these alterations, directly or indirectly via TNF-alpha, is shown. Altered glutamate uptake and catabolism associated with impairment in cell connectivity via MMP/TIMP imbalance could compromise the functional integrity of the CNS in general and that of neurons and oligodendrocytes in particular.

Animals↗
PubMed2000

CD99 engagement: an effective therapeutic strategy for Ewing tumors.

CD99 is a Mr 32,000 transmembrane molecule that shows a high level of expression on cells of the hemopoietic system as well as on Ewing tumor cells. Within the hematopoietic system, CD99 has been implicated in cell adhesion and cell death, participating in this way in the differentiation of T-cell precursors. In this study, we demonstrate that engagement of CD99 significantly inhibits the in vitro and in vivo growth ability of Ewing tumor cells by delivering an apoptotic stimulus and reducing the malignant potential of these cells. Moreover, we show that anti-CD99 monoclonal antibodies may be advantageously used in association with conventional anticancer agents. These results provide a novel entry site for therapeutic intervention, which may have application in the care of patients with Ewing tumor, and warrant additional studies to clarify the molecular mechanisms activated by CD99 engagement.

12E7 Antigen↗
PubMed2000

Src-mediated tyrosine phosphorylation of NR2 subunits of N-methyl-D-aspartate receptors protects from calpain-mediated truncation of their C-terminal domains.

Src-mediated tyrosine phosphorylation of N-methyl-d-aspartate receptor subunits has been shown to modify the functional properties of N-methyl-d-aspartate receptors. Moreover, calpain-mediated truncation of N-methyl-d-aspartate receptor subunits has been found to alter the structure of the receptors. In the present study, we first used immunoprecipitation with a variety of antibodies against N-methyl-d-aspartate receptor subunits and anti-phosphotyrosine antibodies to show that tyrosine-phosphorylated subunits of N-methyl-d-aspartate receptor are protected against calpain-mediated truncation of their C-terminal domains. A GST fusion protein containing the C-terminal domain of NR2A was used to identify the calpain cutting sites in the C-terminal domain. One site was identified at residues 1278-1279, corresponding to one of the preferred calpain truncation sites. This site is adjacent to a consensus sequence for Src-mediated tyrosine phosphorylation, and Src-mediated tyrosine phosphorylation of the GST-NR2A C-terminal fusion protein also inhibited calpain-mediated truncation of the fusion protein. We propose that phosphorylation of NR2 subunits and the resulting inhibition of calpain-mediated truncation of their C-terminal domains provide for the stabilization of the N-methyl-d-aspartate receptors in postsynaptic structures.

Amino Acid Sequence↗
PubMed2000

Differences between family physicians and patients in their knowledge and attitudes regarding traditional chinese medicine.

Background: With patients turning more to alternative medicine, most physicians are still conservative in their views toward these practices. It is important to know whether there is a difference between physicians and patients regarding knowledge and attitudes about alternative medicine. This study focused on information regarding a specific type of alternative medicine, traditional Chinese medicine (TCM). Methods: Two questionnaires-one for physicians, one for patients-were designed. Two clinics were chosen as sites where patients could fill out the questionnaires while they were waiting for treatment. A total of 85 patient questionnaires were collected. Forty-four completed questionnaires were returned from family physicians in Cincinnati area. Data analyiss included t-test, analysis of variance, and logistic regression. Results: Generally, physicians and patients had the same knowledge level on TCM. Physicians, however, had more knowledge on basic concepts, whereas patients knew more about practice, such as the specific conditions that could be treated by TCM. A difference between physicians and patients on attitudes toward TCM was found, with patients having a more positive attitude. More than 60% of the patients in this study had visited alternative practitioners during the year prior to this study. The inform rate was higher for the patients visiting physicians who practiced alternative treatment. Conclusions: There are differences between physicians and patients regarding their knowledge and attitudes about TCM.

Journal Article↗
PubMed2000

T lymphocytes activated by persistent viral infection differentially modify the expression of metalloproteinases and their endogenous inhibitors, TIMPs, in human astrocytes: relevance to HTLV-I-induced neurological disease.

Activation of T lymphocytes by human pathogens is a key step in the development of immune-mediated neurologic diseases. Because of their ability to invade the CNS and their increased secretion of proinflammatory cytokines, activated CD4+ T cells are thought to play a crucial role in pathogenesis. In the present study, we examined the expression of inflammatory mediators the cytokine-induced metalloproteinases (MMP-2, -3, and -9) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3), in human astrocytes in response to activated T cells. We used a model system of CD4+ T lymphocytes activated by persistent viral infection (human T lymphotropic virus, HTLV-I) in transient contact with human astrocytes. Interaction with T cells resulted in increased production of MMP-3 and active MMP-9 in astrocytes despite increased expression of endogenous inhibitors, TIMP-1 and TIMP-3. These data suggest perturbation of the MMP/TIMP balance. These changes in MMP and TIMP expression were mediated, in part, by soluble factors (presumably cytokines) secreted by activated T cells. Integrin-mediated cell adhesion is also involved in the change in MMP level, since blockade of integrin subunits (alpha1, alpha3, alpha5, and beta1) on T cells resulted in less astrocytic MMP-9-induced expression. Interestingly, in CNS tissues from neurological HTLV-I-infected patients, MMP-9 was detected in neural cells within the perivascular space, which is infiltrated by mononuclear cells. Altogether, these data emphasize the importance of the MMP-TIMP axis in the complex interaction between the CNS and invading immune cells in the context of virally mediated T cell activation.

Adult↗
PubMed2000

CD99 (E2) up-regulates alpha4beta1-dependent T cell adhesion to inflamed vascular endothelium under flow conditions.

CD99/E2 is an integral transmembrane protein which forms, together with Xga, a distinct family whose genes are located in the pseudoautosomal region. The number of T cells that firmly bound to vascular endothelial cells under physiological shear stress increased 2-14-fold upon CD99 stimulation, and bound cells became much more resistant to detachment forces and spread. T cell arrest occurred within 1 min and was dependent on the alpha4beta1-VCAM-1 pathway. In contrast, the alphaLbeta2-ICAM-1 pathway remained unactivated. This was observed with T cell lines and with activated peripheral blood lymphocytes, and was limited within the resting peripheral CD4+ T cells to the memory subset, while virgin cells were unaffected. This discloses a stepwise regulation of the T cell extravasation cascade.

12E7 Antigen↗
PubMed2000

Human bronchoalveolar lavage fluid protein two-dimensional database: study of interstitial lung diseases.

Recently, we published an analytical two-dimensional electrophoresis (2-DE) protein map of human bronchoalveolar lavage fluid (BALF) using a pool of BALFs from various patients. In this report, the effect of lung disorders on the protein composition of the lung epithelial lining fluid was investigated by 2-DE of BALFs from individual patients with well-defined interstitial lung diseases: sarcoidosis, idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP), using improved experimental conditions. On these gels, about 600-1000 stained protein spots could be identified in a BALF sample containing 25 microg of protein, and our original human BALF protein database has, therefore, been considerably extended. Altogether, 429 protein spots corresponding to 66 different proteins (including isoforms, protein subunits and fragments) were identified by microsequence analysis and by matching with a human blood plasma 2-DE protein map available in the SWISS-2DPAGE database. A human 2-DE BALF database was established and is available on the World Wide Web (http://www.umh.ac.be/-biochim/proteomic.htm+ ++). The significance of the modifications observed between the different lung pathologies is discussed with the aim of understanding the mechanistic bases of lung disease pathogenesis and finding new potential lung markers of disorders.

Adult↗
PubMed2000

The Near-Infrared (3)Phi --> (1)(3)Delta Transition of LaF.

Rotational analyses of 32 subbands of the near-infrared (3)Phi --> (1)(3)Delta system of LaF have been carried out, involving the levels v = 0-7 of the two states. The three subsystems were first treated as separate singlet systems, directly at equilibrium. Perturbations were revealed in the lower state, ascribed to spin-uncoupling interactions between (1)(3)Delta(3)(v) and (1)(3)Delta(2)(v + 1) levels. A 21 x 21 matrix representation at equilibrium of the complex of interacting levels (v = 0-6) was then constructed, each diagonal v-block corresponding to a triplet model of the rovibrational (3)Delta Hamiltonian. The observed perturbations were completely reduced in the harmonic oscillator approximation with an experimental value of the interaction parameter B(Delta)(0,1) = 0.01322(2) cm(-1). The wavenumbers of some 4500 lines of the system were fitted with an rms error of about 0.005 cm(-1). (Line lists are available in electronic form via http://www-obs.univ-lyon1.fr/~ABernard/index.html.) Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Tubular duplication of the esophagus. Contribution of magnetic resonance imaging in anatomical analysis before surgery.

The authors report a tubular duplication of the thoracic esophagus in a 17-year-old male. This anomaly, rare in the adult, can be explained either by a failure of esotracheal compartmentalisation, or a notochordodysraphy or more probably by an error during vacuolisation of the esophagus. The anatomical characteristics of the duplication were clearly seen on MRI. This investigation showed the intramural duplication, with only a thin barrier without muscle, between the esophageal lumen and the duplication channel: two communications were present between the esophageal lumen and the duplication. The esophagus was accessed by right thoracotomy. The close contact between the duplication and the esophagus did not allow them to be separated. A subtotal esophagectomy was necessary, with digestive continuity being restored by coloplasty after a left cervicotomy and a laparotomy. The anatomy seen on the MRI should have predicted that an esophagectomy was necessary and that a thoracotomy could have been avoided by performing the procedure with a closed thorax.

Adolescent↗
PubMed2000

Identification of prognostic factors determining risk groups for lung resection.

BACKGROUND: Pulmonary resection belongs to a group of surgical procedures with significant morbidity and mortality. The aims of this study were to classify postoperative complications and to identify prognostic factors determining risk group. METHODS: In a prospective study 500 patients undergoing lung resection (wedge resection, n = 141; lobectomies, n = 245; bilobectomies, n = 12; and pneumonectomies, n = 102) were included. In 178 patients (36%) pulmonary resections were extended to structures or thoracic organs. Sleeve resection of the bronchus to preserve lung parenchyma was performed in 22 patients. RESULTS: Classification of postoperative complications fell into four categories: patients without postoperative complications; patients with moderate complications (n = 137); patients with severe complications (n = 38); and death (n = 33). Factors adversely affecting postoperative complications by multivariate analysis included pulmonary pathology, bronchoplastic technique, forced expiratory volume in 1 second (FEV1), extended resection, type of lung resection, comorbidity indices, and preoperative chemotherapy. Four risk groups were determined. Risk group I (n = 60) with the best prognosis included patients with FEV1 greater than or equal to 80% undergoing wedge resection for a benign lesion or metastasis. Risk group II (n = 161) included patients with FEV1 greater than or equal to 80% undergoing major pulmonary resection for a benign lesion or metastasis or lung cancer, or patients with FEV1 less than 80% undergoing wedge resection for benign lesion or metastasis. Risk group III (n = 233) with a fair prognosis included patients with comorbidity indices less than 4 and FEV1 greater than or equal to 80% undergoing extended pulmonary resection for a benign lesion or metastasis or lung cancer, or patients with FEV1 less than 80% and emphysema. Risk group IV (n = 46) with the worst prognosis included patients with FEV1 less than 80% undergoing an extended lung resection or bronchoplastic procedures for a benign lesion or metastasis or lung cancer, or patients with comorbidity indices greater than or equal to 4 undergoing extended lung resection for lung cancer. CONCLUSIONS: In a prospective study, based on these prognostic factors, a practical, easy-to-use risk group system of lung resection is proposed as a tool to aid the decision to perform lung resection.

Adolescent↗
PubMed2000

Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker.

Clara cell protein (CC16) is a 15.8-kDa homodimeric protein secreted in large amounts in airways by the non-ciliated bronchiolar Clara cells. This protein increasingly appears to protect the respiratory tract against oxidative stress and inflammation. In vitro, CC16 has been shown to modulate the production and/or the activity of various mediators of the inflammatory response including PLA2, interferon-gamma and tumour necrosis factor-alpha. CC16 has also been found to inhibit fibroblast migration or to bind various endogenous or exogenous substances such as polychlorobiphenyls (PCBs). This protective role is confirmed by studies on transgenic mice, showing that CC16 deficiency is associated with an increased susceptibility of the lung to viral infections and oxidative stress. In humans, a polymorphism of the CC16 gene, localized to a region linked to airway diseases, has recently been discovered in association with an increased risk of developing childhood asthma. Finally, CC16 also presents a major interest as a peripheral marker for assessing the integrity of the lung epithelium. The determination of CC16 in serum is a new non-invasive test to detect Clara cell damage or an increased epithelial permeability in various acute and chronic lung disorders.

Animals↗