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Biomedical subjects

M Fournier

Publications and source records attributed to M Fournier.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

Phenotyping of beluga whale blood lymphocytes using monoclonal antibodies.

Widespread efforts are currently made to classify morphologically indistinguishable lymphocyte subpopulations in several species. In order to increase the knowledge in cetacean immunology, cross-reactivity of antibodies against bovine, human, ovine and mouse cell surface proteins was tested on beluga whale (Delphinapterus leucas) peripheral blood lymphocytes using flow cytometry. Anti-MHC class I and II as well as anti-CD2 reacted with virtually all peripheral blood lymphocytes. Anti-TCR gamma delta and anti-CD4 reacted with respectively 31% and 30% of peripheral blood lymphocytes. B lymphocytes were identified by an anti-surface IgM which was present on 6% of blood lymphocytes. Specificity of these antibodies was demonstrated by immunoprecipitation of beluga proteins with similar molecular weight to that of other species. These results could be useful for further immunotoxicological evaluation of highly versus mildly contaminated populations of belugas.

Animals↗
PubMedDate not supplied

Purification of functional T lymphocytes from splenocytes of the beluga whales (Delphinapterus leucas).

In an effort to gain knowledge on immune functions in beluga whales, Delphinapterus leucas, we have used two physical methods for the purification of T lymphocytes of spleen cells. Isolation by sheep red blood cells (SRBC) rosetting and by adherence on nylon wool columns were tested. SRBC-rosetting gave unreliable results in obtaining purified T cells. Therefore, the purification of T cells was done using nylon wool columns. Less than 3% of the IgM(+) B cells remained in effluent populations. In the later population, 45% gave positive staining with mouse anti-human CD4 allowing us to verify functionality of the cells. The study of calcium mobilization and tyrosine kinase activation, mediated by CD4 cross-linking permitted verification of the functionality of cells. We also showed that upon activation with mitogens, beluga T cells upregulate the density of MHC class II molecules on their surfaces. CD4 cross-linking with a specific antibody inhibited the proliferation response. Overall, the activation of beluga whales lymphocytes did not differ markedly from what is known in other species. This study can help in the groundwork for functional investigation of the beluga whale's immune system.

Animals↗
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In vitro lymphotoxicity and selective T cell immunotoxicity of high doses of acyclovir and its derivatives in mice.

The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N2-acetyl ACV (ac-ACV) and N2,O-diacetyl ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute number of CD3+, CD8+, and CD25+ cells, but not Ig+ cells, was noted at high concentrations of ACV and its derivatives, suggesting a selective T cell cytotoxicity. Similarly, the in vivo exposure revealed selective T cell immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2+ and CD8+ cells was not accompanied with any marked changes in the Ig+ population. The CD4+/CD8+ ratio was affected both in vitro and in vivo by high concentrations of ACV.

Acyclovir↗
PubMedDate not supplied

In vivo indomethacin reverse exercise-induced immunosuppression in rats.

The effect of oral indomethacin on the immunosuppressive effect of exercise was examined in exercised untrained female Wistar rats immunized with sheep red blood cell (SRBC) antigens. Intensity of the 1 h exercise was controlled by 0-50 kPa air pressure, generated by a compressor located at the bottom of a water tank, during continuous swimming of the rats, previously immunized with SRBC. After 48-72 h, depending on the ip (intraperitoneal) or iv (intravenous) route of SRBC immunization, the exercise suppressed humoral PFC response and augmented phagocytosis of peritoneum macrophages. These effects occurred only when exercise was performed at 48 h after antigen injection. Animals receiving indomethacin, however, did not show any exercise-related suppression of the PFC response. The data suggest a relationship between exercise-induced immunosuppression and possible increased in vivo prostaglandin synthesis during the intense exercise. Overall, exercise-related suppression of humoral PFC response was dependent on the intensity of the exercise, was time specific, and was reversible by pharmacological blockade of the cyclooxygenase pathway of prostaglandin synthesis.

Administration, Oral↗
PubMedDate not supplied

EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium.

Breast cancer is the most frequent cancer in women while it is the second cause of cancer death. Estrogens are well recognized to play the predominant role in breast cancer development and growth and much efforts have been devoted to the blockade of estrogen formation and action. The most widely used therapy of breast cancer which has shown benefits at all stages of the disease is the use of the antiestrogen Tamoxifen. This compound, however, possesses mixed agonist and antagonist activity and major efforts have been devoted to the development of compounds having pure antiestrogenic activity in the mammary gland and endometrium. Such a compound would avoid the problem of stimulation of the endometrium and the risk of endometrial carcinoma. We have thus synthesized an orally active non-steroidal antiestrogen, EM-652 (SCH 57068) and the prodrug EM-800 (SCH57050) which are the most potent of the known antiestrogens. EM-652 is the compound having the highest affinity for the estrogen receptor, including estradiol. It has higher affinity for the ER than ICI 182780, hydroxytamoxifen, raloxifene, droloxifene and hydroxytoremifene. EM-652 has the most potent inhibitory activity on both ER alpha and ER beta compared to any of the other antiestrogens tested. An important aspect of EM-652 is that it inhibits both the AF1 and AF2 functions of both ER alpha and ER beta while the inhibitory action of hydroxytamoxifen is limited to AF2, the ligand-dependent function of the estrogen receptors. AF1 activity is constitutive, ligand-independent and is responsible for mediation of the activity of growth factors and of the ras oncogene and MAP-kinase pathway. EM-652 inhibits Ras-induced transcriptional activity of ER alpha and ER beta and blocks SRC-1-stimulated activity of the two receptors. EM-652 was also found to block the recruitment of SRC-1 at AF1 of ER beta, this ligand-independent activation of AF1 being closely related to phosphorylation of the steroid receptors by protein kinase. Most importantly, the antiestrogen hydroxytamoxifen has no inhibitory effect on the SRC-1-induced ER beta activity while the pure antiestrogen EM-652 completely abolishes this effect, thus strengthening the need to use pure antiestrogens in breast cancer therapy in order to control all known aspects of ER-regulated gene expression. In fact, the absence of blockade of AF2 by hydroxytamoxifen could explain why the benefits of tamoxifen observed up to 5 years become negative at longer time intervals and why resistance develops to tamoxifen. EM-800, the prodrug of EM-652, has been shown to prevent the development of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat, a well-recognized model of human breast cancer. It is of interest that the addition of dehydroepiandrosterone, a precursor of androgens, to EM-800, led to complete inhibition of tumor development in this model. Not only the development, but also the growth of established DMBA-induced mammary carcinoma was inhibited by treatment with EM-800. An inhibitory effect was also observed when medroxyprogesterone was added to treatment with EM-800. Uterine size was reduced to castration levels in the groups of animals treated with EM-800. An almost complete disappearance of estrogen receptors was observed in the uterus, vaginum and tumors in nude mice treated with EM-800. EM-652 was the most potent antiestrogen to inhibit the growth of human breast cancer ZR-75-1, MCF-7 and T-47D cells in vitro when compared with ICI 182780, ICI 164384, hydroxytamoxifen, and droloxifene. Moreover, EM-652 and EM-800 have no stimulatory effect on the basal levels of cell proliferation in the absence of E2 while hydroxytamoxifen and droloxifene had a stimulatory effect on the basal growth of T-47D and ZR-75-1 cells. EM-652 was also the most potent inhibitor of the percentage of cycling cancer cells. (ABSTRACT TRUNCATED)

Animals↗
PubMedDate not supplied

The SCOPE study: health-care consumption related to patients with chronic obstructive pulmonary disease in France.

OBJECTIVE: The main objective of the SCOPE study was to estimate the total direct medical costs of patients with treated chronic obstructive pulmonary disease (COPD) in France according to severity stages. METHODS: Total medical resources consumption of a sample of COPD patients was collected over a 12-month period through a national physician survey (including both general practitioners and lung specialists). This survey was completed for 255 patients. Data were then extrapolated to all patients with diagnosed and treated COPD in France. Average total medical resources consumption of a COPD patient per year was 4366 euros. Among this cost 41% was directly related to COPD follow-up, 25% to COPD-related complications (mainly exacerbations), and 34% to other diseases. More than one-third of the total direct COPD cost was related to hospitalizations and 31% to drug consumption. COPD-related costs increased markedly with severity based on FEV1 (but data suggested the existence of a threshold effect). SCOPE data did not show any evidence of a significant relationship between direct medical cost and patient age, sex, addiction to tobacco, or duration of COPD. The total medical consumption of COPD patients in France was 3.5 billion euros and accounted for 3.5% of the total medical expenditures (prevalence of COPD was estimated 1.3% in the general population). RESULTS: The SCOPE study revealed the high level of medical resources consumption of patients with COPD. CONCLUSIONS: The burden of COPD itself and its complications appeared to be of considerable magnitude in France especially for severe COPD.

Aged↗
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Characterization of the in vitro hepatocyte model for toxicological evaluation: repeated growth stimulation and glutathione response.

Hepatocytes in culture represent a useful model for investigating the effects of toxic agents on liver cells. However, further development of this model is hampered by the difficulty in promoting cell proliferation over prolonged periods and the lack of knowledge about the biochemical status of the cells relevant to the toxic response under proliferation conditions. In an effort to overcome these limitations, this work focused on the establishment of conditions to ameliorate the promotion of hepatocyte proliferation in vitro. It also examined the effects of growth stimuli on the levels of glutathione (GSH), a highly significant parameter influencing the resistance against toxic agents. In addition, albumin secretion was monitored as an indicator of liver-specific functions. Two modified L-15 media were developed: medium A for supporting cell differentiation, and medium B for promotion of proliferation. Collagen and Matrigel were used as substrata. In medium A, the time course of GSH levels was comparable for both substrata, with an initial increase followed by a plateau and then by a progressive decrease from the second to the fourth week. Hepatocytes cultured on collagen and sequentially exposed to medium B (containing epidermal growth factor +/- norepinephrine) and medium A, showed repeated responsiveness to stimulation of DNA synthesis. Moreover, for cultures on collagen, a higher GSH content was observed in parallel with DNA synthesis stimulation, while albumin secretion was diminished. Although cells on Matrigel were refractory to DNA synthesis stimulation, GSH levels were still increased upon exposure to the growth factors, while under these conditions, albumin synthesis remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMedDate not supplied

Immunotoxicity of pesticides: a review.

The intricate balance that is the hallmark of the immune system shows vulnerability to any chemical, including pesticides, that can cause structural and functional alterations to the system. The immunotoxic effects of xenobiotics include: histopathologic effects in immune tissues and organs; cellular pathology; altered maturation of immunocompetent cells; changes in B and T cell subpopulations; and functional alterations of immunocompetent cells. Pesticides, including fungicides, herbicides, and insecticides, are the only class of chemicals deliberately released into the environment because of their toxicity. Around the world, millions of people are exposed to pesticides at work and/or in their home. This article reviews evidence, from animal and human studies, on the effects of pesticides on the immune system.

Animals↗
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[Multicenter Study on Cultural Attitudes and Norms towards Violence (ACTIVA project): methodology].

The purpose of this article is to describe the conceptual bases and methods used in the ACTIVA multicenter study, as well as the process employed in the different stages of the research. General information is given on the approach, design, and methods that were applied in the cities that participated in the study: San Salvador, El Salvador; San José, Costa Rica; Cali, Colombia; Caracas, Venezuela; Salvador, Bahia, Brazil; Rio de Janeiro, Brazil; Santiago, Chile; and Madrid, Spain. The objectives of the study were to: (1) analyze and compare among cities the prevalence of verbal and physical aggressive behaviors toward children, the spouse or other partner, and persons outside the family; and (2) identify personal, environmental, and socioeconomic factors associated with these violent behaviors. The purpose of the ACTIVA project was to generate information to help guide violence-prevention policies and programs in the cities and to provide criteria for decision-making, as well as to obtain baseline data to use in evaluating prevention policies and programs. To achieve the proposed objectives, a single, common questionnaire was prepared and validated. The questionnaire was used in face-to-face interviews with residents of private urban homes who were between 18 and 70 years old. The sample was selected in each city through stratified multistage sampling of clusters proportionate to the socioeconomic strata of the general population and without any substitutions. The final sample consisted of 10,821 people. In general, the response rates were within the established limits. Exceptions included San José, Rio de Janeiro, and Madrid, where the size of the final sample was slightly smaller than anticipated. More young men of higher socioeconomic strata declined to participate, so that the samples had an overrepresentation of women from medium and lower strata. The article concludes with a description of the scope and limitations of the study, in terms of both the approach and methods. With their comparative analyses, studies of this type can contribute to identifying the differences and similarities between cities. The article shows that with this method it is possible to analyze how violent behaviors are associated with different risk factors and individuals' characteristics, at a point in time. However, this design is limited in terms of establishing causal relationships, and it did not allow an evaluation of the context of every specific instance of violence.

Adolescent↗
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[Experimental study of the effect of membrane oxygenators on the pulmonary structure of the dog and monkey (author's transl)].

Six dogs and 5 monkeys were subject to extracorporeal circulations with membrane oxygenators for various time periods (from 4 to 57 hours). The pulmonary samples, examined with electron microscopy, enabled us to control the appearance of lesions (similar for the two animal species) and to follow their evolution. From the second hour, abnormalities of the capillary endothelium were observed; but at the 6th hour, the lesions had already deeply affected the whole pulmonary structure and became more and more serious. This intrinsic toxicity of membrane oxygenators on the pulmonary structure should incite extreme caution in the use of this method in man.

Animals↗
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[Experimental study of extra-corporeal circulation with membrane oxygenators: effects on the lung structures of dogs and monkeys (author's transl)].

Six dogs and 5 monkeys underwent extra-corporeal circulations with membrane oxygenators for variable time periods (from 4 to 57 hours). The development and evolution of the lesions, which were similar in the two animal species, were controlled by electron microscopic examination of lung samples. From the 2nd h, abnormalities of the capillary endothelium were observed; but a 6 h, all the inner lung structures were reached and the lesions grew worse with time. Thus, the intrinsic toxicity of membrane oxygenators on lung structures emphasizes that this method should be used with utmost precaution in man.

Animals↗
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[Bronchiolitis obliterans after lung transplantation].

Lung transplantation has become a realistic treatment in some patients with severe respiratory impairment or severe pulmonary arterial hypertension. Immunosuppression therapy is about the same in all transplantation units and includes cyclosporin, corticosteroids and azathioprine. The diagnosis of acute rejection episodes has been greatly facilitated by the histological study of transbronchial biopsies obtained by endoscopy. Improvements in the short-term prognosis of these patients have made it possible to individualize an unusual and delayed complication: bronchiolitis obliterans. This progressive and diffuse obstruction followed by destruction of the transplant's bronchioles is interpreted as a consequence of chronic rejection. The diagnosis of bronchiolitis obliterans is difficult and rests essentially on degradation of the respiratory function resisting to increased immunosuppression. Some viral infections perhaps contribute to its development, and it may be so severe as to require another lung transplantation.

Bronchiolitis Obliterans↗
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[Interstitial pneumopathies: criteria of drug side-effects. Results of consensus meetings].

Since 1984, the use of the official method for determining the responsibility of drugs in side-effects has been compulsory in France. This method offers, but does not define, different qualificatives for chronological and semeiological criteria. Consensus workshops have been set up to define the undesirable side-effects themselves and the different qualificatives in each of the principal fields of pathology. As regards drug-induced interstitial pneumonia, chest specialists from university hospitals, members of the national system of pharmacovigilance and representatives of the Roussel-Uclaf central department of pharmaco-vigilance have determined: the limits of time elapsed between the beginning and end of drug administration and the occurrence of the adverse reaction; how to interpret various courses of the side-effect with and without temporary discontinuation of the drug, and how to interpret a possible readministration. A list of investigations aimed at excluding the main possible causes of interstitial pneumonia has been drawn up.

Chronology as Topic↗
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[Use of nerve division in oculomotor paralysis].

Sectors have a double interest in an extraocular muscle palsy: to avoid the diplopia and to aid the reeducation of palsied muscles. Patient can alternatively wear the two types of glasses with sectors. Authors decrease sector's size when motility improves. They are stopped if regression, and in other cases, patients can wait surgical time with maximum comfort. Clinical examples are presented: VI, III and IV cranial nerve palsies and generalized diplopia.

Abducens Nerve↗
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Macrophage functional activities versus cellular parameters upon sublethal pesticide exposure in mice.

The toxicity of selected organochlorine, organophosphate, and carbamate pesticides on the functions and cellular parameters of peritoneal macrophages was examined in inbred C57Bl/6 mice. Effects of single, sublethal pesticide exposure on macrophages were determined by analysis of the cell viability, cell adherence capacity, generation of superoxide anion (O2-), antigen processing, phagocytosis of Salmonella typhimurium, and resistance to in vitro virus-induced cytopathic effects (cpe) after infection with mouse hepatitis virus 3 (MHV3). Most of the studies were done for the organochlorine pesticide dieldrin, which inhibited several macrophage functions, such as phagocytosis of S. typhimurium, release of the single processed protein antigen avidin, and resistance to MHV3 virus-induced cpe. The virus-induced cytolysis in macrophage cultures was significantly increased after in vivo exposure to single sublethal doses of other selected pesticides, such as guthion, carbofuran, sevin, and matacil. However, none of the selected pesticides, used in sublethal (0.4 less than or equal to LD50 less than or equal to 0.6) doses appeared to be a factor impairing the O2- -generating system in chemically elicited or immunologically activated peritoneal macrophages. In conclusion, sublethal pesticide exposure can induce a significant impairement of several macrophage functions, such as phagocytosis, antigen processing, and resistance to virus-induced cytolysis. Inhibition of the O2- -generating system by sublethal pesticide exposure, however, can be excluded as a mechanism of potential suppressory action of these pesticides on antiviral and antibacterial host defence systems in which macrophages play a primary role.

Animals↗
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Morphological changes in rat tracheal mucosa immediately after antigen challenge.

We have investigated the morphological effects of an intratracheal challenge with 50 micrograms ovalbumin (OA) on sensitized rat tracheas, in vivo. Female Sprague-Dawley rats were primed ten days before challenge with a single i.t. injection of 100 micrograms OA plus Bordetella pertussis (OA-BP). Two additional groups of animals served as controls: primed animals challenged with saline only and non-primed but OA-challenged animals. Sacrifices--and subsequent morphological studies--were performed prior to and 5, 15 and 60 min after challenge. At each time, the total numbers of epithelial nuclei, subepithelial mast cells (SEMC) and intraepithelial mast cells (IEMC) were scored in six non-adjacent cross sections per trachea. We found that: 1) priming with OA-BP alone did not induce any change in the tracheal mucosa with respect to morphological structure and mast cell counts; 2) no morphological change nor significant modification of the cell counts occurred at any time in tracheas from either of the control groups; 3) in contrast, a luminal heterogeneous exudate and a subepithelial oedema developed in 9 of the 15 tracheas of primed animals within 60 min of OA challenge. In those nine tracheas, the scores of intraepithelial nuclei, of IEMC and of SEMC were found to decrease significantly 15 min after challenge as compared with starting values (p less than 0.05 for each score). The decrease in the number of mucosal mast cells is probably related to the damages of the epithelial cells and to the difficulty with which depleted mast cells can be seen by toluidine blue staining.

Animals↗
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[The role of thymic microenvironment in T-cell maturation].

The role played by different components of thymic microenvironment in T-cell-maturation is examined: antibodies to a soluble thymic factor (STF) were thus shown to inhibit T-cell maturation in the chicken while incubation of bursal "null" cells with STF could induce the differentiation of some of them into T cells. In addition to STF, whose properties resemble those of other soluble thymic factors, an insoluble thymic factor (ITF) is described: it is localized mainly in membranes associated with medullary blood vessels, and its injection to mice provokes an influx of marrow stem cells into the thymus.

Animals↗