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A Bergeron

Publications and source records attributed to A Bergeron.

At least 37 records · Page 2Linked to original sources
PubMed1999

The death factors: a combinatorial analysis.

This paper presents theoretical and computational tools to understand how a small group of proteins, the death factors, are involved in widely different behavior of the cell. Experiments were done using a virtual laboratory that can simulate cellular response to different external stimuli. WARNING: It is not certain which of the theoretical protein clusters described here really occur in nature. In addition, the rules of cluster assembly are combinatorial, and thus an oversimplification to describe the real situation.

Animals↗
PubMed1998

Spatial disparity coding in the superior colliculus of the cat.

Cells in the superficial layers of the superior colliculus of the cat have mainly binocular receptive fields. The aim of the present experiment was to investigate the sensitivity of these cells to horizontal spatial disparity. Unit recordings were carried out in the superficial layers of the superior colliculus of paralyzed and anesthetized cats. Centrally located receptive fields were mapped, separated using prisms, and then stimulated simultaneously using two luminous bars optimally adjusted to the size of the excitatory region of the receptive fields. Only binocular cells were tested, and 65% of these units were found to be sensitive to spatial disparities. Some cells (20%) were clearly insensitive to spatial disparity and the remaining 15% showed complex, unclassifiable interactions. The sensitive cells could be divided into four classes based on their disparity-sensitivity profiles: 38% showed excitatory interactions, whereas 9% showed inhibitory interactions. Moreover, 11% and 7% of the cells responded, respectively, to crossed or uncrossed disparities, and were classified as near cells and far cells. Whereas the general shapes of the sensitivity profiles were similar to those of cells in areas 17-18, selectivity in the superior colliculus was significantly coarser. The superficial layers of the superior colliculus project topographically to the deep layers of the superior colliculus, which are known to contain circuits involved in the control of ocular movements. The results thus suggest that disparity-sensitive cells of the superior colliculus could feed information to these oculomotor neurons, allowing for the localization and fixation of objects on the appropriate plane of vision.

Animals↗
PubMed1998

Spatial and temporal matching of receptive field properties of binocular cells in area 19 of the cat.

The spatial and temporal properties of single neurons were investigated in area 19 of the cat. We evaluated the matching of binocular receptive field properties with regard to the respective strength of the ipsilateral and contralateral inputs. Results indicate that most cells in area 19 are well tuned to spatial and temporal frequencies and exhibit relatively low contrast threshold (mean=6.8%) when assessed using optimal parameters and tested through the dominant eye. Spatial resolution (mean=0.75 c/degree), optimal spatial frequencies (mean=0.16 c/degree) were relatively low and spatial bandwidths (mean=2.1 octaves) were broader as compared to those of cells in area 17 but comparable to those of cells in other extrastriate areas. On the other hand temporal resolution (mean=10.7 Hz), optimal temporal frequency (mean=4.5 Hz) and temporal bandwidths (mean=2.9 octaves) were higher and broader than in primary visual cortex. A significant relationship exists between most of the cell's properties assessed through either eye. For some parameters, such as spatial and temporal resolution, ocular dominance was shown to be significantly related to the extent of matching between the two eyes. For these parameters, binocular cells that exhibited a balanced ocular dominance were generally well matched with regard to the receptive field properties of each eye whereas the largest mismatches were found in cells that were more strongly dominated by one eye. These results suggest that visual input contributes to the activation of cells in area 19 in a redundant manner, possibly attesting to the multiplicity of parallel pathways to this area in the cat.

Animals↗
PubMed1998

Relapsing nodular lesions in the course of adult pulmonary Langerhans cell histiocytosis.

In most patients with pulmonary Langerhans cell histiocytosis (LCH), clinical and radiological abnormalities initially either stabilize or regress, often without treatment. Little information is available, however, concerning the subsequent evolution of disease in patients who initially follow a benign course. We describe four patients with biopsy-confirmed pulmonary LCH whose initial course was characterized by regression of parenchymal nodular lesions, but who subsequently developed one or more episodes of active disease 7 mo to 7.5 yr after their initial presentation. In each case, the subsequent episodes of active disease were characterized by the reappearance or marked increase in nodular radiographic abnormalities, whose presence was confirmed by high-resolution computed tomography (HRCT). Thus, initial regression of nodular lesions in pulmonary LCH does not preclude the reappearance of one or more episodes of active disease, and may have important consequences on the long-term prognosis of these patients.

Adult↗
PubMed1997

Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response.

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.

Adult↗
PubMed1997

Influence of spatial configuration on the expression of carcinoembryonic antigen and mucin antigens in human bladder cancer.

CEA and cellular mucin antigens have been recognized as potential targets for specific immunotherapy and are frequently expressed in bladder cancer. We studied the coordinated expression of a bladder cancer-associated CEA glycoform and of the mucins MUC1, MUC2 and MAUB under various growth conditions in the MGH-U3 bladder-cancer cell line. CEA and MUC2 mRNAs and proteins were detected in nude mouse tumors and spheroids but not in monolayer cultures. Expression of MAUB and bladder-cancer CEA also was induced according to spatial configuration of cells. MUC1 was always expressed under various growth conditions, but its glycosylation was modulated: in spheroids and mostly in tumor cells, the SM3 protein epitope was unmasked and sialyl-Tn was induced. The kinetics of modulation of MAUB and bladder-cancer CEA were different. The epitope recognized by the monoclonal antibody (MAb) 19A211 was rapidly induced in the aggregation phase of spheroid formation and rapidly lost upon plating of tumor cells, suggesting a relationship with cell contact. By contrast, MAUB induction in spheroids was delayed to the compaction phase, when cell aggregates become resistant to disruption, and loss of expression upon tumor plating occurred slowly over several culture passages. No induction of these 2 antigens was observed in the presence of differentiation agents, endothelial cell products or interferon-gamma, but it occurred when MGH-U3 cells were cultured at high density on extracellular matrix. Our results suggest that CEA and mucin antigen expression in bladder cancer is modulated by the spatial configuration of cells.

Animals↗
PubMed1997

Biochemical analysis of a bladder-cancer-associated mucin: structural features and epitope characterization.

Three monoclonal antibodies (mAbs), M344, M300 and M75, were shown to define a unique tumour-associated antigen (TAA) of superficial bladder tumours. The antigenic determinants are expressed on a very-high-molecular-mass component and, in about 50% of the positive samples, one determinant is also detected on a 62 kDa molecular species, observed only under reducing conditions. The objectives of the present study were to characterize further this TAA by analysing (1) the biochemical nature of the epitopes recognized by the three mAbs, and (2) the biochemical and structural features of the molecule bearing them. The antigenicity was resistant to heat denaturation, trypsin and alpha-chymotrypsin treatments but highly sensitive to papain and Pronase digestion. NaIO4 oxidation decreased reactivity to mAbs M344 and M300 but enhanced reactivity to mAb M75. The three determinants were insensitive to beta-galactosidase and alpha-L-fucosidase but were sensitive to Vibrio cholerae neuraminidase. None of the three mAbs reacted with ovine, bovine or porcine submaxillary mucins. Deglycosylation with O-glycosidase or trifluoromethanesulphonic acid completely abolished the reactivity of the mAbs whereas N-glycosidase F deglycosylation had no appreciable effect. The presence on the molecule of cryptic Gal(beta(1-3))GalNAc as a major core disaccharide was demonstrated by a heterologous sandwich assay using mAb M75 and peanut agglutinin. Thiol reduction using beta-mercaptoethanol increased mobility of the high-molecular-mass component in polyacrylamide gels. We thus conclude that mAbs M344 and M300 react with sialylated carbohydrate epitopes, and mAb M75 reacts with a partially cryptic and periodate-resistant sialylated epitope expressed on a typical secreted high-molecular-mass oligomeric mucin which we named MAUB for mucin antigen of the urinary bladder.

Animals↗
PubMed1997

Spatial resolution and contrast sensitivity of single neurons in area 19 of split-chiasm cats: a comparison with primary visual cortex.

Electrophysiological recordings were carried out in the callosal recipient zone of area 19 in normal and split-chiasm cats and, for comparison purposes, at the border of areas 17 and 18 of split-chiasm cats. The influences of retinothalamic and callosal inputs on a single cortical neurons were thereby evaluated. Extracellular recordings of single cells were made in anaesthetized and paralysed cats in the zone representing the central visual field. Receptive field properties were assessed using sine wave gratings drifting in optimal directions. Results showed that in area 19 and areas 17/18 one-third of the cells were binocularly driven after section of the optic chiasm. In area 19, the spatial resolution and contrast sensitivity of cells driven via the dominant eye were similar in the normal and split-chiasm groups. In areas 17/18 and area 19 of split-chiasm cats, binocular cells showed significant interocular matching of their receptive field properties (spatial resolution and contrast threshold), although small differences were observed. These small interocular differences were related to the cell's ocular dominance rather than to the signal transmission route (thalamic or callosal).

Animals↗
PubMed1997

Combinatorial tools for the analysis of transcriptional regulation.

In this paper, we discuss virtual experiments for the study of major regulatory processes such as translation, signalization or transcription pathways. An essential part of these processes is the formation of protein clusters held together by a small number of binding domains that can be shared by many different proteins. Analysis of these clusters is complicated by the vast number of different arrangements of proteins that can trigger a specific reaction. We propose combinatorial tools that can help predict the effects on the rate of transcription of either changes in transcriptional factors concentration, or due to the introduction of chimeras combining domains not usually present on a protein.

Computer Simulation↗
PubMed1996

Spatial and temporal frequency tuning and contrast sensitivity of single neurons in area 21a of the cat.

The spatial and temporal selectivities of single neurons in area 21a of the adult cat were investigated using sinusoidal gratings. Optimal spatial frequencies and visual acuity (high cut-off frequency) were fairly low and spatial bandwidth was mainly narrow. Contrast threshold was generally low but a substantial number of cells were only excited by high contrast stimuli. The temporal selectivity suggests that cells responded to a wide range of temporal frequencies.

Animals↗
PubMed1996

MAUB is a new mucin antigen associated with bladder cancer.

The M344 tumor-associated antigen, expressed in 70% of superficial bladder tumors, is a sialylated carbohydrate present on a high molecular mass thiol-reducible secreted mucin, which we named MAUB for mucin antigen of the urinary bladder. Herein we studied the relationship between MAUB and other known mucins in the MGH-U3 bladder cancer line where MAUB expression is modulated by culture conditions. Northern blots, immunoradiometric assays, and Western blots showed that only MUC1 and MUC2 are expressed in this MAUB-positive cell line. MUC1 differs from MAUB by its molecular mass and its non-oligomeric nature, while MUC2 has similar molecular mass and response to culture conditions. However, in double determinant immunoradiometric assays, MAUB and MUC2 did not cross-react. Moreover, confocal microscopy showed different subcellular localization of the two antigens. Treatment of MGH-U3 cells with MUC2 antisense oligodeoxynucleotides resulted in decreased expression of MUC2 and increased expression of MAUB, ruling out the possibility that monoclonal antibody M344 recognizes a different glycosylated form of MUC2. In addition, we identified a tumor specimen expressing MAUB but no MUC2 antigen or mRNA. Together, these results suggest that there is expression of at least three mucins in MGH-U3 cells and that MAUB is a cancer-associated mucin distinct from those identified so far.

Animals↗
PubMed1996

Identification of a superficial bladder tumor-associated glycoform of the carcinoembryonic antigen by monoclonal antibody 19A211.

Monoclonal antibody (mAb) 19A211 identifies a superficial bladder cancer-associated sialylated epitope expressed on a heterogeneous group of glycoproteins. These glycoproteins consist of a series of cytoplasmic glycoproteins ranging from 90 to 140 kDa present in tumor cells and, at a lower level, in normal urothelial cells, and of a membrane glycoprotein of 200 kDa observed in tumor cells only. To further characterize this antigenic system, we took advantage of the high avidity of mAb 19A211 to produce a rabbit polyclonal antibody by immunizing with antigen bound to mAb 19A211 immunoaffinity beads. The resulting polyclonal antibody specifically reacts with the 200-kDa species and not with the other glycoproteins. The biochemical characterization of this 200-kDa tumor-associated antigen showed that it is highly glycosylated (more than 50% w/w) and is anchored to the membrane via a glycosyl phosphatidylinositol link; these properties are shared with the carcinoembryonic antigen (CEA). Further experiments showed reactivity of two mAbs directed against protein epitopes of CEA with the 200-kDa component of 19A211 antigen. However, in immunohistochemistry studies of 29 colon and 23 bladder tumor specimens, no correlation was observed between expression of 19A211 and CEA antigens. Moreover, in RIAs, the intensity of expression of the 19A211 carbohydrate epitope relative to a CEA protein epitope was found to be significantly lower with CEA purified from a colon cancer cell line compared to CEA from a bladder cancer cell line. On the basis of these results, we conclude that the 200-kDa component of 19A211 antigen is a CEA glycoform preferentially expressed by superficial bladder tumors.

Animals↗
PubMed1996

Role of granulocyte-macrophage colony stimulating factor (GM-CSF) in the pathogenesis of adult pulmonary histiocytosis X.

BACKGROUND: Pulmonary histiocytosis X is a disorder characterised by the presence of destructive granulomas preferentially involving distal bronchioles, that contain numerous activated Langerhans' cells. Recent studies have shown that granulocyte-macrophage colony stimulating factor (GM-CSF), which is produced by normal bronchiolar epithelium, may play an important part in the distribution and differentiation of Langerhans' cells. The aim of this study was to evaluate the role of this factor in the pathogenesis of pulmonary histiocytosis X. METHODS: Four patients with pulmonary histiocytosis X were examined by immunohistochemical techniques for GM-CSF and CD1a surface molecules. RESULTS: In early lesions the epithelium of bronchioles affected by the disease was strongly positive for GM-CSF and infiltrated by numerous CD1a+ Langerhans' cells organised into granulomas. In contrast, the expression of GM-CSF was substantially lower in bronchioles not affected by the disease, and these bronchioles contained few Langerhans' cells. When destruction by histiocytosis X lesions was more advanced, only remnants of bronchiolar epithelium could occasionally be identified; these remained strongly reactive for GM-CSF. Langerhans' cells within granulomas also moderately expressed this cytokine. CONCLUSIONS: These results support the hypothesis that GM-CSF could be one of the factors responsible for the local accumulation of lymphostimulatory Langerhans' cells in early lesions of pulmonary histiocytosis X.

Adult↗
PubMed1995

Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose-response study and comparison with prostacyclin.

To investigate the capacity of the pulmonary vascular bed to acutely vasodilate, we examined in 35 consecutive patients with primary pulmonary hypertension (PPH), the hemodynamic effects of incremental inhalation periods of an air-NO mixture at different concentrations (10, 20, and 40 ppm), and compared them with those of an acute infusion of prostacyclin (PGI2). An individual pulmonary vasodilator response was defined by a fall in total pulmonary resistance (TPR) > or = 30% relative to mean TPR baseline value. Thirteen patients were responders and 22 were nonresponders to both drugs, and they did not significantly differ in overall baseline characteristics except for mean right atrial pressure (p < 0.03). In responders, both drugs produced similar individual vasodilator response. Changes in mean pulmonary arterial pressure and TPR observed during NO and PGI2 were closely correlated (r2 = 0.9, p < 0.001, and r2 = 0.7, p < 0.01, respectively). The vasodilator response to NO was not concentration-related with a maximal effect obtained at 10 ppm. Combination of both drugs did not lead to any additive vasodilator response. Unlike PGI2, NO did not induce any systemic effect, no adverse reaction, but a moderate increase in methemoglobin. Inhaled NO at low dose (10 ppm) appears to be an effective, safe, and reliable substitute for PGI2 in screening for acute pulmonary vasodilator responsiveness during therapeutic assessment of patients with PPH.

Adult↗
PubMed1995

Enhanced metabolism of LDL aggregates mediated by specific human monocyte IgG Fc receptors.

Macrophage-derived foam cells are important constituents of atheromatous lesions. In addition to the scavenger receptor pathway, uptake of immune complexed lipoproteins through IgG Fc receptors (Fc gamma receptors) represents an additional pathway of macrophage foam cell development that may be important during atherogenesis. The importance of this mechanism is suggested by studies showing that the titer of autoantibodies to modified lipoproteins correlated with the extent of occlusive disease in patients, and that those antibodies exist in human lesions. Human mononuclear phagocytes possess three structurally and functionally distinct classes of Fc gamma receptors, each of which could be associated with a unique pathway of lipoprotein metabolism. In order to determine whether uptake of an acute lipid load through each type of Fc gamma receptor was associated with foam cell development, we used bispecific antibodies consisting of anti-LDL monoclonal antibodies conjugated to anti-Fc gamma receptor monoclonal antibodies to study the effects of targeting LDL aggregates to each specific type of Fc gamma receptor on freshly isolated adherent human monocytes. Relative to appropriate controls, LDL degradation, cellular sterol mass, and foam cell development of monocytes were enhanced by targeting LDL aggregates to Fc gamma RI or Fc gamma RII, and this was accompanied by an apparent impairment of LDL degradation. Uptake was specific to the Fc gamma receptors and was not influenced by the presence of scavenger receptor ligands. Thus, with the bispecific approach, the functions of each class of Fc gamma receptor can be studied on an individual basis with respect to several aspects of cellular cholesterol metabolism. This will be critical for determining which of these receptors are potentially most important in the clearance of lipoprotein immune complexes during atherogenesis.

Antibodies, Bispecific↗
PubMed1993

Cloning and characterisation of an aminopeptidase P-encoding gene from Streptomyces lividans.

An aminopeptidase P (PepP)-encoding gene has been cloned from Streptomyces lividans 66 by screening for overexpression of activity using the chromogenic substrate Gly-Pro-beta-naphthylamide as a liquid overlayer on colonies growing on agar medium. The pepP gene was localised by deletion mapping, and the nucleotide sequence was determined. The deduced amino acid sequence was found to display significant similarity to Escherichia coli PepP. The partially purified S. lividans enzyme had a 50-kDa subunit and was present as a homodimer. Direct Edman degradation of the purified protein confirmed that pepP encoded the observed intracellular PepP.

Amino Acid Sequence↗