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Biomedical subjects

F Laurent

Publications and source records attributed to F Laurent.

At least 19 recordsLinked to original sources

[Effects of toxins, apamine, charybdotoxin and iberiotoxin on the relaxation of the smooth muscular fiber induced by imidazo(1,2-a)pyrazine derivative].

Experiments have been performed in order to analyse the mechanism whereby SCA40, a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. We investigated the effect of different toxins, known to be K(+)-channel blockers on guinea-pig smooth muscle relaxant activity of SCA40. The small conductance Ca(2+)-activated K(+)-channel blocker apamin (100 nM) did not antagonize the relaxant activity of SCA40 in 1 microM carbachol-contracted isolated guinea pig trachea. The large conductance Ca(2+)-activated K(+)-channel blocker, iberiotoxin (30, 60 and 180 nM) antagonized the relaxant activity of SCA40 in an apparently competitive manner. The concentration-relaxation curves to SCA40 were shifted to the right with no significant alteration in the maximum response. The relaxant activity of SCA40 in 1 microM carbachol-contracted isolated trachea was antagonized by both charybdotoxin (60 nM) and iberiotoxin (60 nM), but the antagonism induced by iberiotoxin appears to be more potent than that induced by charybdotoxin. It is concluded that the potent relaxant activity of SCA40 on guinea-pig airway smooth muscle in vitro involves a charybdotoxin and iberiotoxin sensitive K(+)-channel.

Animals

Synthesis and antibronchospastic activity of 8-alkoxy- and 8-(alkylamino)imidazo[1,2-a]pyrazines.

Theophylline still occupies a dominant place in asthma therapy. Unfortunately its adverse central nervous system (CNS) stimulant effects can dramatically limit its use, and adjustments in the dosage are often needed. We have synthesized a new series of imidazo[1,2-alpha]pyrazine derivatives which are much more potent bronchodilators than theophylline in vivo and do not exhibit the CNS stimulatory profile. In vitro studies on isolated rat uterus and guinea pig trachea confirm the high potentialities of these derivatives. 6-Bromo-8-(methylamino)imidazo[1,2-alpha]-pyrazine-3-carbonitrile (23) is identified as the most potent compound of the series. As in the case of theophylline, phosphodiesterase inhibition appears unlikely to be the unique mechanism of action of this series of heterocycles.

Animals

[Importance of PCR in the diagnosis of hepatitis C].

The identification of hepatitis C virus, based on DNA amplification, gives a precise estimation of the prevalence of the most frequent agent of NANB hepatitis. The first ELISA allowing the detection of anti-HCV antibodies, had too many false positive results and required the development of more sensitive and specific assays to confirm its results. PCR, allowing the hepatitis C virus diagnosis by showing directly HCV RNA sequences, offers a complementary approach to immunoserological tests. In blood donors with anti-HCV antibodies and with indeterminate or negative confirmatory tests, the finding of HCV RNA sequences reveals serum infectivity. During acute hepatitis, the delay in the appearance of anti HCV hampers acute phase diagnosis. The early detection of HCV RNA in peripheral blood, confirms the diagnosis and opens up therapeutic possibilities. In chronic hepatitis, the diagnosis of seronegative forms may only be resolved by PCR. Moreover, the presence of HCV RNA in peripheral blood represents the only marker of on-going viral replication and coincides with the severity of liver damage. During treatment with interferon, the follow up of HCV RNA sequences makes it possible to monitor its efficacy. The search for HCV RNA sequences directly in liver tissue shows that HCV may replicate in the liver in the absence of viremia. The presence of HCV RNA in the liver and the serum of liver transplanted patients is essential for the etiological diagnosis and management of hepatitis and bone marrow failure occurring after transplantation. Epidemiological study using PCR is a major tool in documenting vertical transmission between mother and child. Finally, PCR is important for the analysis of the HCV genome. Thus, in France there are at least three main strains, one close to the US prototype, the other close to the Japanese strain, possibly responsible for a more severe illness and a third one distinct from the previous two. However, its limits and constraints imply that PCR must not be considered as a routine assay. This emphasizes the need for more simple and rapid diagnostic tests, allowing the detection of HCV antigens and, as in hepatitis B, the progressive unravelling of the life cycle of HCV.

Animals

Rapid detection of members of the family Enterobacteriaceae by a monoclonal antibody.

Six monoclonal antibodies directed against enterobacteria were produced and characterized. The specificity of one of these antibodies (CX9/15; immunoglobulin G2a) was studied by indirect immunofluorescence against 259 enterobacterial strains and 125 other gram-negative bacteria. All of the enterobacteria were specifically recognized, the only exception being Erwinia chrysanthemi (one strain tested). Bacteria not belonging to members of the family Enterobacteriaceae were not detected, except for Plesiomonas shigelloides (two strains tested), Aeromonas hydrophila (five strains tested), and Aeromonas sobria (one strain tested). This recognition spectrum strongly suggested that CX9/15 recognized the enterobacterial common antigen. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) experiments, the six antienterobacteria antibodies presented similar specificities; they all revealed only one band with an apparent molecular weight of about 20,000 from the crude extract of an enterobacterium. The six monoclonal antibodies, and especially CX9/15, can be used to develop new tests for rapid and specific detection of enterobacteria.

Antibodies, Monoclonal

Lung density and lung mass in emphysema.

Mean lung density (dm) and radiologic (VLx) lung volume can be calculated using CT scan data. As many emphysematous patients are overdistended, the analysis of dm alone could be meaningless. However, lung mass (m) can be calculated as the product of dm and VLx. Twenty-four patients suspected of mild or severe emphysema as judged by roentgenographic and physiologic examinations as well as 16 healthy subjects were included in the protocol. They all underwent both a CT scan of the whole lung and functional tests from which the following were derived: airway resistance, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC), CO transfer capacity, quasi-static compliance at functional residual capacity (FRC), and blood gases. All CT scans were performed at the FRC of each patient. The dm was lower in emphysema patients than in healthy subjects, as m was greater in patients than in healthy subjects; 1,303 +/- 398 g and 997 +/- 133 g, respectively. Although dm values were significantly correlated to FEV1, FEV1/FVC, and TLC, m values were not correlated to any of these functional indices. Unexpectedly, these results show that most patients (22/24) with emphysema have a normal or increased lung mass. Normal or above normal m values might be due to oversecretion in some patients. Nevertheless, the synthesis of new tissue due to chronic inflammation is the most likely explanation that could account for this finding.

Adult

Influence of bovine somatotropin on the composition and manufacturing properties of milk.

Three studies (84, 140, and 200 d) were performed to examine the effect of injecting dairy cows with various doses (0, 320, 640, or 960 mg/28 d; 0 or 640 mg/28 d; 0, 320 mg/14 d, or 320 or 640 mg/28 d) of bST on milk production, composition, and manufacturing properties. Mean bST response among studies on milk production varied from 0 (trial 1) to 7.3% (trial 2) and from 8.5 to 14.2% (trial 3) in relation to feeding conditions. Neither milk fat nor protein percentages in milk at time of maximum response were affected by the use of bST. Distribution of casein and protein in the whey was not affected by the treatments at any time. The nature of fatty acids varied more with time after injection than with bST doses. Neither coagulation time, standard curd firmness, nor soft or pressed cheese yields were affected by the treatments.

Animals

[Primary mediastinal choriocarcinoma. Apropos of 3 cases].

We report three cases about the diagnostic imaging features of mediastinal choriocarcinoma and during follow up. Computed tomography proved to be more accurate than plain X ray to show the topography and volume of the mediastinal mass hence providing a better approach for biopsy and surgical ablation of the residual tumoral tissues. However, CT cannot differentiate fibrous tumoral remnants from active malignancies and beta HCG is an important tumoral marker in the follow up.

Adult

[Non-invasive imaging in aortic dissection].

Previously with a drastic prognosis, aortic dissection has extensively benefitted from advances in medical and surgical treatment, as well as progress in methods of investigation. While aortography is classically the reference special investigation, non-invasive methods now have a place of choice both during the acute phase (transthoracic and transesophageal echocardiography) and the chronic phase or for the purpose of post-operative monitoring (CT scan, magnetic resonance imaging). In an emergency context, the most important point is to diagnose a type A dissection, involving the ascending aorta, the treatment of which is surgical. In the majority of cases the diagnosis can now be made on the basis of transthoracic and transesophageal echocardiographic findings, which also enable identification of the site of the portal of entry, extension and concomitant lesions, all important features to be taken into consideration regarding surgical tactics.

Aortic Dissection

[Biological and developmental aspects of macronodular adrenal hyperplasia in Cushing's disease].

The pathophysiology of macronodular adrenocortical hyperplasia (MNH) associated with Cushing's diseases remains debatable. Some authors have claimed that MNH represents an autonomous condition that has to be treated by surgical adrenalectomy while others advocate the use of pituitary surgery. We have compared the biochemical features, before and after pituitary surgery, between 7 cases of MHN and 22 cases of diffuse hyperplasia (DH) associated with Cushing's disease. In addition, the diameter of the adrenal nodules after surgery was evaluated in 6 cases. The mean ACTH level in MNH and DH subjects was similar. Dexamethasone suppressibility and the stimulatory effect of metyrapone on ACTH secretion were less in MNH than in DH subjects, suggesting a greater degree of adrenal autonomy in the former. The cortisol responses to metyrapone and CRF tests suggested an increased responsiveness of the adrenals to endogenous ACTH in the MNH group. Only one MNH patient had biochemical features suggesting a primary adrenal disease. The use of a sensitive ACTH assay and the results of inferior petrosal sinus sampling identified the ACTH-dependency of the disease. A short to medium term remission of the disease was obtained in all cases of MNH and in 87% of cases of DH after surgery. The diameter of the adrenal nodules significantly decreased in only 43% of cases. Our results suggest that the adrenal autonomy in MNH is incomplete and that, despite the persistence of the adrenocortical nodules, the disease can be cured with pituitary microsurgery in most cases.

Adrenal Glands

[How can intrathoracic lymphatic involvement be assessed: does tomography have a role? What is the contribution of computed tomography and MRI?].

The authors report their analysis of the literature on the evaluation of intrathoracic extension of non-small-cell bronchial cancers to lymph nodes, using tomography, computed tomography and magnetic resonance imaging. The criteria used to assess the metastatic character of a lymph node, the characteristics of the populations studied and the methods of comparison with the clinicopathological "truth" account for the variations of the results published. Tomographs are useless today. The performances of CT and MRI are equivalent, and it is not necessary to associate both techniques. Although its performances are mediocre, CT allows mapping the mediastinal lymph nodes, which is useful to continue the assessment of extension and to make decisions.

Carcinoma, Non-Small-Cell Lung

Selective detection of human hepatitis B virus surface and core antigens in some peripheral blood mononuclear cell subsets by flow cytometry.

The presence of HBs and HBc antigens was investigated, by flow cytometry, on the surface of peripheral mononuclear cells (PBMC) from the following phenotype: CD3 (T lymphocytes), CD4 (T helper/inducer), CD8 (T cytotoxic/suppressor), CD19 (B lymphocytes) and CD56 (NK cells) among 8 patients suffering from chronic hepatitis B and 5 healthy HBV-negative subjects. This study demonstrated the presence of HBsAg and HBcAg on the lymphocyte surface for most of the patients. The mean percentage of labelled cells was 17% for HBsAg and 15% for HBcAg. Among the different lymphocyte subsets only B lymphocytes and the NK cells expressed HBsAg for 57% and 26% of cells, respectively. Similarly HBcAg was also detected among CD19 and CD56 cells only. PCR was used to search for the presence of HBV DNA and RNA in PBMC, using primers located in the S gene. HBV DNA was detected with variable intensity in the CD3, CD4, CD19 and CD56 subsets following their separation with a cell sorter. For HBV RNA the signal obtained after PCR and Southern blotting was higher for CD56 and CD19 cells than for CD3 cells and undetectable for CD4 cells. This study demonstrates that replication and transcription can occur in CD19 and CD56 cells. Positive signals in CD3 cells may possibly be due to contamination of this subpopulation by NK cells.

Antigens, CD

Oxidative metabolism of polymorphonuclear leukocytes: modulation by adhesive stimuli.

Different agents such as phorbol myristate acetate (PMA), N-formyl-methionyl-leucylphenylalanine (fMet-Leu-Phe), or opsonized zymosan induced an oxidative burst in rat peritoneal polymorphonuclear leukocytes (PMNs) elicited by casein. Plastic adhesion of PMNs down-regulated superoxide (O2) release stimulated by PMA or fMet-Leu-Phe but had no effect on zymosan-induced O2 generation, indicating that the O2 forming enzyme, the NADPH oxidase, was not affected by modulation and that a common step of the transductional events induced by PMA or fMet-Leu-Phe might be involved in this regulation. We demonstrated that a differential translocation of protein kinase C (PKC) was not responsible for that modulation. PMA-induced secretion of granule content (vitamin B12-binding protein) was not susceptible to modulation, suggesting that the transductional pathways leading to O2 generation and granule secretion are partly separated. The adhesion of PMNs to different substrates (glass, plastic, albumin-, laminin-, fibronectin-, poly-lysine-, or concanavalin A-coated plastic) down-regulated to different extent superoxide release. Whether the nature of the biochemical signal induced by the diverse adhesive stimuli or a physical parameter such as binding strength was involved in this differential behavior remains to be elucidated. Since adhesiveness was dependent on the state of the cytoskeleton and O2 inducers were reported to stimulate actin polymerization, we studied the F-actin content and distribution of PMNs by using the specific fluorescent probe NBD-phallacidin and an original methodology allowing a quantitative analysis of fluorescence on both adherent and suspended cells. PMA induced a polarization of F-actin on suspended PMNs but had no effect on the intracellular distribution of F-actin in adherent PMNs. Thus, we suggest that the adhesion of PMNs induced an immobilization of F-actin, possibly correlated to the down-regulation of one of the transductional pathways involved in the NADPH oxidase activation.

Actins

Diagnosis and categorization of small bowel neoplasms: role of computed tomography.

A retrospective study of 35 patients with small bowel neoplasms studied by computed tomography (CT) was performed. The tumor detection rate was 80%. Using the findings reported in the literature, an adequate histological diagnosis could be performed in 69% of the cases by CT. Lipomas, leiomyomas, leiomyosarcomas, and carcinoid tumors were well-recognized, but adenocarcinomas and lymphomas were often mistaken one for the other. An accurate preoperative staging was performed in 61% of the cases. CT failed to detect 75% of the invaded lymph nodes, 25% of the liver metastases, and 25% of the tumoral growth beyond the bowel wall. Despite major limitations in preoperative staging, a good detection rate and some features allowing a specific diagnosis advocate using CT along with the barium examination when clinical history suggests a small bowel tumor.

Adenocarcinoma

[Myocardial mass index in the diagnosis of acute rejection of allogeneic heart transplants].

Changes in an index of left ventricular mass were evaluated in the diagnosis of acute cardiac transplant rejection in a prospective study involving 28 transplant patients by comparison with the histology of endomyocardial biopsy. The surface of a ring of left ventricular myocardium obtained from a 2D echocardiographic examination was used as an index of mass. Eighty-three pairs of results--biopsy and index of mass--recorded within a 12 hour interval were obtained between the first day and 10th month of transplantation over a period of 12 consecutive months. Echocardiographic diagnosis of acute rejection was made when the index of myocardial mass increased by over 7 per cent compared with baseline values recorded during the first 3 days of transplantation or during a new period of equilibrium after an episode of rejection. Two groups of patients were identified from the results of biopsy, taken as the reference: in 16 patients with mild or moderate histological signs of rejection the variation of the index of mass was 18.3 +/- 9.1%; endomyocardial biopsy was negative in the 12 other patients and the change in index of mass was -1.5 +/- 5.2% (p less than 0.001). The overall concordance in the 83 successive results was good with a Kappa coefficient of 0.71. The other parameters which have been reported to be useful in diagnosing rejection (relaxation, antegrade diastolic mitral flow, acoustic density of myocardium) present a number of problems in routine practice related either to difficulties with the recording of the data or to its interpretation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

[Imaging of malignant lymphoma of muscular sites].

Seventeen cases of muscular lymphoma are reported (5 primary non-Hodgkin lymphoma, 11 secondary NHL, 1 secondary Hodgkin's disease). The psoas or gluteus muscle was involved in 10 cases, and the lower limb was affected in the remaining 7 cases. Nine cases of muscular extension of bone NHL are also reported. On sonograms these lesions were always large and less echogenic than adjacent structures, with no signs of necrosis before treatment. US and CT patterns were comparable for both primary and secondary lesions, regardless of the type of lymphoma or whether or not there was any previous bone lesion. Associated lymphomatous lesions were observed in 14 cases. On angiograms, muscular lymphomatous involvement presented a hypovascular pattern. While ultrasonography is an excellent monitoring technique for soft tissue lymphomas (specially for the lower limbs), a major contribution of CT is the detection and the follow-up of deep or thoracic wall lesions.

Adolescent

[Tomodensitometric aspects of brain lymphomas: apropos of 19 cases. Brain lymphoma].

The authors present the results of CT studies for 19 patients with cerebral lymphoma (including 12 primary tumors). CT appearances varied considerably, because 5 of the 12 primary lymphomas presented as multifocal lesions, and lesion sites included the corpus callosum (3 cases), the central caudate nucleus (4 cases), the posterior fossa (3 cases), and the cerebral hemispheres (6 cases). These findings are in agreement with literature data. Although a solitary, hyperdense and homogeneous lesion in the corpus callosum or the central caudate nucleus is indicative of cerebral lymphoma, numerous other aspects are possible and owing to the increasing frequency of this pathology should suggest this diagnosis. There is no specific appearance for secondary lymphomas, but diagnosis is often facilitated by concomitant systemic involvement.

Adult

[Contribution of x-ray computed tomography and MRI to the surgical diagnosis of bronchial cancers. Comparative evaluation of x-ray computed tomography, MRI and thoracotomy in 111 cases].

Computed tomography and magnetic resonance imaging have respectively decreased the incidence of exploratory thoracotomy by 11.6% to 5.7% then 5.3% after their successive inclusion in the assessment of the operability of lung cancers. Based on a systematic comparison of CT and MRI with exploratory thoracotomy in 111 patients, the yield, sensitivity and positive predictive value of these examinations was assessed in relation to tumour extension to various sites: to the chest wall, for which the sensitivity was poor (38% for CT, 54% for MRI) with a moderate predictive value (71% for CT, 77% for MRI); to the mediastinum with improved sensitivity (69% and 72%) but an uncertain predictive value (61% and 72%). The sensitivity and predictive value were then measured for lymph node involvement: N1: moderate sensitivity (69% and 76%) but a good predictive value (95% and 92%); N2 and N3: good sensitivity (79% and 93%) but a poor predictive value (70% and 66%). Apart from a few particular indications specific to MRI, especially in the apex, left hilum and in contact with the atrium, the efficacy of these two investigations is very similar. However, their lack of specificity means that certain exploratory thoracotomies are still justified in order to assess the operability of the tumour. A surgical or mediastinoscopic anatomical assessment is still necessary for a good classification of lymph node extension of lung tumours.

Carcinoma, Bronchogenic