[Unilateral choroid metastasis revealing bronchial adenocarcinoma in a woman].
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Adenocarcinoma↗
Biomedical subjects
M Fournier
Publications and source records attributed to M Fournier.
Immune functions in beluga whales (Delphinapterus leucas): evaluation of phagocytosis and respiratory burst with peripheral blood leukocytes using flow cytometry.
Flow cytometric assays using peripheral blood were developed to study phagocytosis and respiratory burst, the two major functions of neutrophils and among the most important non-specific defense mechanisms, in beluga whales. The use of flow cytometry avoids the problems associated with the isolation and purification of different cell types, and allows the measurement of a large number of cells (10,000) in a very short period of time. The methods described will be used to compare these functions in blood samples from highly contaminated beluga whales from the St. Lawrence and from relatively clean arctic beluga whales.
Animals↗
Decreased interleukin-2 receptor and cell cycle changes in murine lymphocytes exposed in vitro to low doses of cadmium chloride.
Relationships between in vitro cadmium-related cell cytotoxicity, ultrastructural changes and altered cell cycle were determined at 21-72 h after mitogenic stimulation of C57BL/6 mouse spleen lymphocytes with concanavalin A (Con A). Relatively low doses, 0.6-10 microM cadmium (Cd), added at 4 h after the mitogen activation, induced a significant cell cytotoxicity and reduced the lymphoblastic activity of the cells. Cytometric analysis of the lymphoid cell cycle at 72 h revealed that at concentrations > or = 0.6 microM Cd, the number of cells arrested in G0 + G1 phase increased, whereas the proportions of cells of the S and G2 + M phases were substantially reduced. Staining of cells with fluorescent anti-CD25 monoclonal antibody showed a cadmium-related decreased number and relative mean fluorescence of CD25+ cells, demonstrating a decreased level of interleukin-2 receptor (IL-2R). Furthermore, immunogold ultramicroscopic assay was developed for determination of intracellular interleukin-2 (IL-2) in cadmium-treated lymphocytes. The level of cytoplasmic and nuclear IL-2, localized in situ by colloidal gold ultraimmunocytochemical technique, has been estimated as markedly decreased in cells treated with > or = 1.2 microM Cd, as compared with the untreated controls. Disorganization/fragmentation of mitochondrion cristae and dilatation of cisternae of the Golgi apparatus appeared as the major ultrastructural change in 1.2 microM Cd-treated lymphocytes. Interestingly, addition of cadmium in the incubation medium, up to 4 h after mitogen activation, also interacted with lymphoproliferative mechanisms of cells in G0 + G1, S and G2 + M phase. Overall, multiple ultrastructural changes of Cd-treated lymphoid cells were clearly related with the reduced cell viability and reduced number of activated lymphoblasts.
Animals↗
Immunoactivating potential of multilamellar liposome vesicles (MLV) in murine popliteal lymph node (PLN) test.
Immunoactivating properties of subcutaneously injected small unilamellar vesicles (SUV) and multilamellar liposome vesicles (MLV) were studied in relation to different transition temperatures (Tc) of phospholipids. Liposome-induced proliferative reaction in the popliteal lymph node (PLN) was quantified by subsequent cytometric assay. Early cell activation during the onset of PLN reaction was monitored by immunophenotyping of lymphocyte subsets stained with a panel of monoclonal antibodies (mAbs) and gating the subset-specific large/activated cells. Injection of MLV liposomes containing distearoyl phosphatidylcholine (DSPC) and dipalmityl phosphatidylcholine (DPPC), characterized by relatively high Tc, resulted in a marked PLN reaction, increased numbers of CD4+, CD8+, Ig+ subsets and increased proportions of large/activated EAM+ (CD69+) and CD25+ (IL-2 receptor+) cells. The reaction was dose and time dependent. In contrast, injection of MLV liposomes containing lipids of low Tc, such as egg phosphatidylcholine (egg PC) and dimyristoyl phosphatidylcholine (DMPC), did not show any immunoactivation. In addition, there was a highly reduced immunoactivating potential of small-size SUV liposomes over large-sized MLV of identical phospholipid composition. Generally, both lipid composition and vesicle size appeared to be essential for the immunoactivating potential of liposomes. The data suggest a possible correlation between the Tc of the phospholipid and the immunoactivating potential of the large-sized MLV liposomes.
Adjuvants, Immunologic↗
Cytometric profile of molybdenum-induced contact sensitization versus a strong allergen reaction to oxazolone in murine auricular lymph node (ALN) test.
Induction of contact hypersensitivity (CH) by molybdenum chloride (MoCl5) was determined by auricular lymph node (ALN) test in C57B1/6 mice. The ALN test was further improved by immunophenotyping and cytometric analysis of subset-specific cell in the draining node. Skin sensitization was induced by topical ear exposure to 1.0-50% oxazolone and resulted in a strong dose-related ALN reaction. Analogous exposure to MoCl5 resulted in a weaker but marked dose-related reaction, also manifested as an increase in cell number/ALN. Other differences between the oxazolone-induced strong sensitization and the MoCl5-related ALN reaction were: (1) an increase in the total number of Ig+ cells, which was, however, unchanged in the MoCl5-exposed mice; (2) a significant increase in the total number of large/activated T-cell subsets; and (3) a marked shift in the relative percentage of gated large/activated subsets of ALN cells, which was not observed in the MoCl5-exposed animals. Thus, it appeared that the molybdenum exposure induced a nonspecific increase in the cell number/ALN and was not accompanied by any marked activation of the T-cell subsets. Immunotoxicity of a 14 day subchronic exposure to MoCl5 at 1-100 ppm in food was studied by quantification of splenic humoral IgM response to sheep erythrocytes (SRBC). Plaque-forming cells (PFC) and enzyme-linked immunosorbent assay (ELISA) revealed unchanged humoral exposure in MoCl5-exposed mice. Cytometric assay of fluorescent beads uptake showed unchanged phagocytic activity of peritoneal macrophages from the MoCl5-exposed mice. Immunophenotyping of CD4+, CD8+, Thy 1.2+ and Ig+ cells revealed no effect of MoCl5 exposure on the total count of cell subsets in the ungated populations of spleen, lymph nodes and peripheral blood cells. Molybdenum chloride should thus be considered as a non-immunotoxic and a weak, nonspecific contact irritant.
Adjuvants, Immunologic↗
Myelin P0 glycoprotein: identification of the site phosphorylated in vitro and in vivo by endogenous protein kinases.
Myelin membrane prepared from mouse sciatic nerve possesses both kinase and substrates to incorporate [32P]PO4(3-) from [gamma-32P]ATP into protein constituents. Among these, P0 glycoprotein is the major phosphorylated species. To identify the phosphorylated sites, P0 protein was in vitro phosphorylated, purified, and cleaved by CNBr. Two 32P-phosphopeptides were isolated by HPLC. The exact localization of the sequences around the phosphorylated sites was determined. The comparison with rat P0 sequence revealed, besides a Lys172 to Arg substitution, that in the first peptide, two serine residues (Ser176 and Ser181) were phosphorylated, Ser176 appearing to be modified subsequently to Ser181. In the second peptide, Ser197, Ser199, and Ser204 were phosphorylated. All these serines are clustered in the C-terminal region of P0 protein. This in vitro study served as the basis for the identification of the in vivo phosphorylation sites of the C terminal region of P0. We found that, in vivo, Ser181 and Ser176 are not phosphorylated, whereas Ser197, Ser199, Ser204, Ser208, and Ser214 are modified to various extents. Our results strongly suggest that the phosphorylation of these serine residues alters the secondary structure of this domain. Such a structural perturbation could play an important role in myelin compaction at the dense line level.
Adenosine Triphosphate↗
Cloning of porcine cytokine-specific cDNAs and detection of porcine tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-1 beta gene expression by reverse transcription PCR and chemiluminescence hybridization.
A reverse transcription PCR assay with porcine cytokine-specific primers was developed to clone cDNA fragments and generate cDNA probes that were specific for porcine tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-1 beta. The specificities of the cDNA PCR products were confirmed by sequence analysis on the basis of known porcine cytokine gene sequences. The reverse transcription PCR assay was also used to study cytokine mRNA expression in lipopolysaccharide (LPS)-stimulated and control unstimulated porcine alveolar macrophages. The cDNA products were analyzed in ethidium bromide-stained agarose gels, and the transcription level of each cytokine was determined relative to the endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RNA level of each cytokine by measuring the intensity of the chemiluminescence hybridization signals by densitometric scanning. Various levels of cytokine mRNAs were detected in both LPS-stimulated and control unstimulated cells. Thus, TNF-alpha mRNA levels were enhanced in the cell cultures stimulated for 6 h with LPS compared with those in control cell cultures. No differences in TNF-alpha transcription levels between LPS-stimulated and control cells were observed after incubation for 24 or 55 h. Enhancements of IL-6 and IL-1 beta mRNA levels were also observed in the cultures stimulated with LPS for 6 and 24 h compared with the cytokine mRNA levels in control cell cultures. The presence of cytokine mRNA transcripts in the LPS-stimulated macrophage cultures correlated with the detection of these soluble cytokines by the bioassays. In contrast, no soluble cytokine was detected in control macrophage culture supernatants in the presence of cytokine mRNA transcripts.
Animals↗
Congestive heart failure: differential adaptation of the diaphragm and latissimus dorsi.
Diaphragm and latissimus dorsi muscle functions, histochemistries, and morphometries were studied in anesthetized male Yucatan minipigs with congestive heart failure (CHF) induced by supraventricular tachycardia (n = 5). Sham-operated animals served as a control group (n = 5). In CHF animals, transdiaphragmatic pressure measured during supramaximal phrenic stimulation was reduced by 40% at low frequencies (< or = 20 Hz) and by 60% at higher frequencies. Twitch amplitude and half-relaxation time were also decreased. The cross-sectional areas of type I, IIa, and IIb fibers were reduced in the diaphragm. The proportion of type I fibers increased, whereas type IIa fibers decreased. Succinate dehydrogenase activity was elevated in type IIa and IIb fibers, but diaphragmatic fatigability was not altered. CHF reduced latissimus dorsi isometric force by 40% for stimulation frequencies > or = 30 Hz. The cross-sectional area of latissimus dorsi type IIb fibers was decreased, but twitch characteristics, fiber type composition, succinate dehydrogenase activity, and fatigability were unchanged. Experimental CHF appears to cause greater intrinsic adaptive changes in the diaphragm compared with those in the latissimus dorsi in the minipig. For both muscles, reduced contractile function was associated with atrophy. Impaired performance of the diaphragm may also be attributed to an increase in the relative contribution of type I fibers to the total tension-generating capacity of the muscle and to the pathophysiological mechanisms underlying the shortened relaxation time of the twitch response.
Adaptation, Physiological↗
Mucosal T-lymphocytes in central airways of lung transplant recipients.
The immunohistochemical profile of mucosal lymphocytes was investigated in the central airways of lung transplant recipients. Bronchial and transbronchial biopsies (BB and TBB, respectively) and bronchoalveolar lavage for culture of bacteria and viruses were performed during a fibroscopic procedure in patients without evidence of chronic rejection, 3 to 10 mo after surgery. Analysis was restricted to samples without concurrent airway infection: 23 pairs of BB and TBB from 18 transplant recipients were analyzed. An immunohistochemical technique was used to identify and score mucosal cells that reacted with monoclonal antibodies against CD4, CD8, CD45-Ro (memory T-cells), and HLA-DR molecules. The same procedure was applied in nine nonsmoking control subjects (NS group). Data from transplant recipients were allocated to R+ (n = 11) or R- groups (n = 12), depending on the presence or absence of histologic evidence of acute rejection on TBB. A statistically significant depletion of every immunoreactive cell subset was observed in the R+ and the R- groups, but not in the NS group. Conversely, no significant difference for either score of immunoreactive cells were found between R+ and R- groups. The immunosuppressive regimen is suspected to play to play a major role in this depletion of bronchial mucosal T-cells. The acute lung rejection process does not appear to affect concurrently the immunohistochemical profile of immunoreactive cells in the bronchial mucosa.
Biopsy↗
Pulmonary reimplantation response in single-lung transplantation.
We studied the characteristics of the pulmonary reimplantation response (PRR) in single-lung transplantation (SLT), and detailed the occurrence, evolution, prognosis and risk factors of this complication. Forty single-lung transplant recipients were studied. Twenty four patients developed hypoxaemia and allograft infiltrates consistent with the PRR. In 40% of the cases hypoxaemia was severe, precluding weaning and requiring prolonged mechanical ventilation with high fractional inspiratory oxygen (FIO2). The mean duration of ventilation was 7 days (range 1-19 days). Clearing of the chest radiographs was progressive, with complete resolution between 6 and 21 days. In all cases, the pulmonary arterial wedge pressure was normal (6 +/- 2 mmHg) suggesting low pressure oedema. Sampling of the pulmonary oedema fluid revealed that the ratio of protein concentration in oedema fluid to that in serum exceeded 0.5. In patients with severe PRR (40% of cases) clinical, radiographic and haemodynamic abnormalities were identical to adult respiratory distress syndrome (ARDS), but the prognosis was more favourable with no death directly related to PRR in our patients. The mean duration of graft ischaemia of the oedematous grafts (241 +/- 103 min) was significantly longer than that of nonoedematous grafts (155 +/- 71 min). These date suggest that prolongation of graft ischaemia increased the incidence of PRR.
Female↗
Possible mechanisms of action of environmental contaminants on St. Lawrence beluga whales (Delphinapterus leucas).
A small isolated population of beluga whales (Delphinapterus leucas) that are highly contaminated by pollutants, mostly of industrial origin, resides in the St. Lawrence estuary, Québec, Canada. Overhunting in the first half of the century was the probable cause for this population to dwindle from several thousand animals to the current estimate of 500. The failure of the population to recover might be due to contamination by organochlorine compounds, which are known to lead to reproductive failure and immunosuppression in domestic and laboratory animals and seals. Functional and morphological changes have been demonstrated in thyroid gland and adrenal cortex in many species exposed to organochlorinated compounds, including seals. Morphological lesions, although different, were also found in belugas. Functional evaluation of thyroid and adrenal glands of contaminated (St. Lawrence) versus much less contaminated (Arctic) belugas is currently under way. Necropsy of St. Lawrence belugas showed numerous severe and disseminated infections with rather mildly pathogenic bacteria, which suggests immunosuppression. Organochlorine compounds and other contaminants found in beluga whales cause immunosuppression in a variety of animal species including seals. Thirty-seven percent of all the tumors reported in cetaceans were observed in St. Lawrence beluga whales. This could be explained by two different mechanisms: high exposure to environmental carcinogens and suppression of immunosurveillance against tumors. Overall, St. Lawrence belugas might well represent the risk associated with long-term exposure to pollutants present in their environment and might be a good model to predict health problems that could emerge in highly exposed human populations over time.
Adrenal Cortex↗
Approaches to the evaluation of chemical-induced immunotoxicity.
The immune system plays a crucial role in maintaining health; however, accumulating evidence indicates that this system can be the target for immunotoxic effects caused by a variety of chemicals including the environmental pollutants of polychlorinated biphenyls, chlorinated dibenzo-p-dioxins, pesticides, and heavy metals. Adverse chemical-induced immunomodulation, which is studied within the discipline of immunotoxicology, may be expressed either as immunosuppression/immunodepression or immunoenhancement. The former may be manifested either as decreased resistance to opportunistic viral, bacterial, fungal, and other infectious agents or increased susceptibility to cancer. Immunoenhancement on the other hand may either increase the risk of autoimmune reactions or result in allergic reactions. This paper attempts to integrate several aspects of the immune system that are relevant to the assessment of potentially immunotoxic chemicals.
Animals↗
Immunotoxicity of heavy metals in relation to Great Lakes.
Heavy metals including mercury, lead, and cadmium are present throughout the ecosystem and are detectable in small amounts in the Great Lakes water and fish. The main route of exposure of humans to these metals is via the ingestion of contaminated food, especially fish. Extensive experimental investigations indicated that heavy metals alter a number of parameters of the host's immune system and lead to increased susceptibility to infections, autoimmune diseases, and allergic manifestations. The existing limited epidemiologic data and data derived from in vitro systems in which human peripheral blood leukocytes were used suggested that the human immune system may also be at increased risk following exposure to these metals. The magnitude of the risk that the presence of such metals in the Great Lakes may pose to the human immune system, and consequently to their health, is not known. In this review, the available data with respect to potential adverse effects of heavy metals on the immune system of humans and experimental animals are discussed, and additional data requirements are suggested.
Adolescent↗
[Mortality due to bronchopulmonary cancers in workers of 2 foundries].
A mortality study was carried out in two factories producing stainless steel in order to assess lung cancer risk among workers employed in coke oven, blast and open hearth furnaces, foundry, electric furnace, hot and cold rolling mills and pickling areas. Occupational exposures of interest were chromium compounds, nickel compounds, polycyclic aromatic hydrocarbons (PAH), silica and asbestos. All male workers having at least one year of employment between 01.01.1960 and 31.12.1990 were followed up for mortality. The vital status was assessed from birth place registries. Complete job histories since date of first employment were abstracted from the company files. The smoking habits of 50% of the cohort members were known from medical records. The observed number of deaths (obs) were compared with the expected ones based on regional rates with adjustment for age, sex and calendar time (Standardized Mortality Ratio, SMR). The cohorts included 6324 (factory 1) and 5270 (factory 2) workers. The overall mortality did not differ markedly from that expected in both factories: SMR = 0.95 (obs = 1540, p = 0.05) in factory 1 and SMR = 1.06 (obs = 916, non-significant) in factory 2. SMRs for lung cancer did not differ from unity, respectively 0.99 (obs = 105) and 1.00 (obs = 54), in whole cohorts. Non-significant lung cancer excesses were observed among workers of some workshops where exposures of interest might have occurred: coke oven (SMR = 2.04), blast furnace (SMR = 1.36), open hearth furnace (SMR = 1.75), hot rolling mills (SMR = 1.29). These processes, however, are no longer involved in the study factories. Furthermore, no lung cancer excess was observed among workers employed in current workshops: electric furnaces and cold rolling mills.
Adult↗
[Post-lung transplantation bronchiolitis obliterans].
Bronchiolitis obliterans is an anatomical lesion with multiple aetiologies. In the lung transplant patient the pure forms of bronchiolitis obliterans are probably the consequence of a process of chronic rejection; in fact necropsy tissue or lungs removed which have been transplanted show that the lesions of bronchiolitis obliterans are often associated with parenchymal disorders, vascular and proximal bronchial disease, which are sequelae of phenomena of rejection or infection. The effect of bronchiolitis obliterans on lung function is constant; this may appear progressively or in stages. Increasing immunosuppressive treatment may arrest the progress. This rarely occurs and the development of respiratory failure tends to be the rule. It is exceptional to achieve the diagnosis of bronchiolitis obliterans from the examination of a transbronchial biopsy. It is a combination of features, both clinical and respiratory function, negative bacteriology and virological investigations as well as the absence of any efficacy of conventional treatment for rejection which leads to the diagnosis. In certain cases the question of a pulmonary re-transplantation is raised.
Bronchiolitis Obliterans↗
[Single-lung transplant in chronic obstructive disease].
The feasibility and the good immediate acceptability of unilateral lung transplants in the patients with obstructive respiratory problems have recently been demonstrated and since the initial reports, some hundreds of lung transplants have been performed in various parts of the world for this indication. Nevertheless, few results of respiratory function are currently available in the medium term. We report these in a series of 20 patients with severe obstruction who were given single lung transplants. The actual probability of survival for 1 and 2 years was 75 and 70% respectively with 4 peri-operative deaths and 2 later deaths. In the 16 survivors of more than 6 months, in relation to the pre-operative values, a significant improvement was observed 3 months after the graft in the FEV1 which rose from 17 +/- 6 to 53 +/- 13% of the predicted values. The PaO2 rose from 52 +/- 10 to 81 +/- 3 mmHg. The distance covered on the six minute walking test went from 99 +/- 84 m before the graft to 587 +/- 147 m 6 months after the operation. In addition to the improved distance, the lung function was stable in a group of patients as the months went by, although there was a fall in the respiratory function in others with the appearance of the syndrome of bronchiolitis obliterans or in 2 patients with bronchial complications. The four patients with severe deterioration in the graft function were re-transplanted with a good clinical result in three of them, the fourth dying in the immediate post-operative period. We conclude that single lung transplant represents an effective treatment both in the short and medium term in patients with chronic airflow obstruction.
Adult↗
Pathology and toxicology of beluga whales from the St. Lawrence Estuary, Quebec, Canada. Past, present and future.
An indigenous population of 450-500 beluga whales (Delphinapterus leucas) inhabiting the St. Lawrence Estuary has been exposed chronically for more than 50 years to a complex mixture of industrial pollutants including organochlorinated compounds (OC), polycyclic aromatic hydrocarbons (PAH) and heavy metals. From 1983 to 1990, we have necropsied 45 well preserved carcasses out of a total of 120 beluga whales reported dead over this period. Of these 45 animals, nine were affected by 10 malignant neoplasms. Fifteen animals (33%) were affected by pneumonia. Milk production was compromised in eight of 17 mature females (41%), by inflammatory changes (seven animals) and cancer (one animal) which affected the mammary glands. Opportunistic bacteria were found in pure culture, and/or in significant amounts in at least two organs in 20 belugas (44%). The concentrations of both total PCBs and highly chlorinated PCB congeners were much higher in St. Lawrence animals than in Arctic beluga whales. OC-induced immunosuppression has been repeatedly demonstrated in a wide variety of animal species. Therefore, it is probable that the immune functions of St. Lawrence beluga whales are impaired. Benzo[a]pyrene adducts were detected in 10 of the 11 St. Lawrence beluga whales of which tissues (six livers, 10/11 brains) were analyzed by a method based on HPLC. No such adducts were found in four Arctic animals. Since benzo[alpha]pyrene is one of the most potent chemical carcinogens known to man, these compounds might be responsible for some of the cancers observed in that population. Overall, our findings contrast vividly with those of others who found that cancers are exceedingly rare in free-ranging odontocete populations and that the major causes for mortalities in these populations are bacteria, parasites, and trauma.
Animals↗
Blockage of thymic medullary epithelial cell activation: in vivo consequences.
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Animals↗