Search PubMed⌕ Search

Biomedical subjects

A Danguy

Publications and source records attributed to A Danguy.

At least 55 records · Page 3Linked to original sources

Determination of proliferative activity in nasal polyps.

AIMS: To determine the level of proliferative activity in 39 nasal polyps with clear cut distinct clinical behaviour patterns. METHODS: The 39 nasal polyps included 11 polyps labelled as "single" and taken from the lateral nasal wall and the middle turbinate; 12 polyps labelled as "massive" and relating to diffuse polyposis involving the entire nasal cavity; six polyps labelled as "ASA" and relating to nasal polyps from patients with acetylsalicylic acid intolerance and asthma; and 10 polyps from cystic fibrosis related polyposis. Cell proliferation was determined by two independent methods: first, the computer assisted microscope analysis of isolated Feulgen stained nuclei for the measurement of the percentage of cells in the S phase of the cell cycle; and second, the immunohistochemical evaluation of a proliferation associated protein by means of the MIB 1 monoclonal antibody. RESULTS: The cystic fibrosis related polyposis exhibited the highest proliferative activity of all the clinically identified nasal polyp groups. Acute inflammatory nasal polyps exhibited a higher cell proliferation than chronic ones. The results also show that while the immunohistochemical determination of cell proliferation by means of the MIB 1 monoclonal antibody is a valuable tool in determining cell proliferation in nasal polyps, the cytometrical image analysis of Feulgen stained nuclei is not useful for this purpose. CONCLUSION: Cell proliferation activity identifies cystic fibrosis as being distinct from the other nasal polyp groups.

Acute Disease↗

Algorithm analysis of lectin glycohistochemistry and Feulgen cytometry for a new classification of nasal polyposis.

The aim of this study is to present a new classification of nasal polyps. This classification is based both on morphologic criteria relating to morphonuclear features from isolated Feulgen-stained nuclei and on glycohistochemical characteristics from histologic slides submitted to three lectins (peanut, wheat germ, and gorse seed agglutinins) and one neoglycoconjugate glycohistochemical stain. While the morphonuclear features (including 30 variables) relate essentially to chromatin pattern, the glycohistochemical stains (including 16 variables) are linked to the presence of specific carbohydrate moieties in cell membranes and cytoplasm. Forty-nine nasal polyps, including single polyps, diffuse polyposis, cystic fibrosis-related polyposis, and aspirin idiosyncracy-related polyposis associated with asthma, were thus characterized. All the variables were obtained quantitatively by means of computer-assisted microscopy. Two complementary methods of data classification were used to determine the actual diagnostic value contributed by each quantitative variable, namely, discriminant analysis, which forms part of multifactorial statistical analysis, and the decision tree technique, which is an artificial intelligence-related algorithm. The data so obtained show that our morphologic classification of nasal polyps fits in with the classification of nasal polyps defined on the basis of clinical criteria.

Algorithms↗

Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.

OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

Adult↗

Influence of gastrin on human astrocytic tumor cell proliferation.

BACKGROUND: Gastrin and cholecystokinin (CCK) mediate their effects through at least two types of receptors (CCK receptors A and B). While it has been hypothesized that gastrin, a stimulator of gastric acid secretion, is also a neurotransmitter and a stimulator of cell proliferation in various normal and neoplastic tissues, its effect on astrocytic brain tumors has not been actively investigated. PURPOSE: Our goal was to determine the effects of gastrin and gastin and/or CCK antagonists on the proliferation in vitro of astrocytic tumor cells by use of both established cell lines and primary cell cultures of tumor tissue. METHODS: Ten established astrocytic tumor cell lines, SW1088, SW1783, Hs683, H4, U87, U118, U138, U373, T98G, and A172, were studied. The effects of added gastrin (at 0.01, 0.1, and microM) and the gastrin/CCK antagonists L-365,260, CI-988, L-364,718, and JMV 234 (each at 0.01, 0.1, and 1 microM) on the cellular proliferation rates of the 10 cell lines were indirectly measured by use of the colorimetric tetrazolium assay. The influence of gastrin (at 0.01 microM) on the cellular proliferation of primary cultures from nine freshly explanted astrocytic tumors was assessed by means of tritiated thymidine uptake and autoradiography. RESULTS: At specific concentrations, added gastrin increased the cellular proliferation of three established astrocytic cell lines (A172, Hs683, and SW1088), decreased it in two (U373 and T98G), and was without effect on the remaining five. Gastrin decreased cellular proliferation in one primary astrocytic tumor cell culture, stimulated it in five, and had no apparent effect in the remaining three. L-365,260, a CCK receptor B antagonist used at 0.01 microM, increased cellular proliferation in seven cell lines (A172, H4, Hs683, SW1783, T98G, U118, and U138), decreased it in one (U87), and had no effect in the remaining two. CI-988, another CCK receptor B antagonist used at 0.01 microM, inhibited cellular proliferation in five cell lines (A172, H4, SW1783, U373, and U87), stimulated it in two (T98G and U138), and had no effect in three. The CCK receptor A antagonists L-364,718 and JMV 234, both used at 0.01 microM, affected the cellular proliferation of only three of the 10 cell lines. CONCLUSIONS: These results suggest that gastrin (and perhaps CCK that belongs to the same peptide family) may play a role in the growth of a substantial proportion of human astrocytic tumors.

Amino Acid Sequence↗

Computer-assisted microscope characterization of BCNU-induced modifications in the collective behavior of 12 human brain cancer cell lines.

The aim of our study is to characterize the disturbance induced by repeated BCNU treatments in 12 human brain tumor cell lines in terms of their collective behavior. This collective behavior was characterized by means of the Delaunay triangulation and Voronoi mathematical paving techniques combined with the computer-assisted microscope analysis of Feulgen-stained nuclei. This methodology enabled growth to be characterized in terms of cell colony size and density. In addition to this colony pattern characterization, the DNA ploidy level was assessed by means of DNA histogram typing. The cell proliferation level was also determined. Ten astrocytic and two medulloblastoma cell lines treated weekly with BCNU were analyzed. Study of the cell colony architecture and cell proliferation revealed specific BCNU-induced modifications in connection with the origins of the cell lines, i.e. astrocytoma (AST), glioblastoma (GBM), or medulloblastoma (MED). The BCNU-induced effect on GBM (the more malignant of the cell lines) was very different in that proliferation was weakened, but the cell colony density increased after a latency phase. The decrease in cell colony density and cell proliferation of MED seems to indicate that they are more sensitive to BCNU than GBM, but relatively tolerant of this type of chemotherapy in comparison with AST.

Brain Neoplasms↗

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: relationship with prostatic specific antigen immunostain and nuclear DNA content.

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Adenocarcinoma↗

The influence of gastrin and/or cholecystokinin antagonists on the proliferation of three human astrocytic tumor cell lines.

We have investigated the potential role of gastrin in the regulation of cell growth in human astrocytic tumors. To this end we have used synthetic analogs of gastrin and cholecystokinin (CCK) which behave as gastrin and/or CCK antagonists, e.g. compounds JMV-97, JMV-209 and JMV-179. Their effects on astrocytic tumor cell proliferation was investigated by the use of the colorimetric MTT assay. The in vitro biological models used in the present study included the SW1088, U87 and U373 astrocytic tumor cell lines. The results demonstrated marked influence of gastrin and CCK antagonists in the regulation of astrocytic tumor growth. This suggests that gastrin and/or CCK antagonists might be tested in experimental glioblastoma.

Astrocytes↗

Neurotensin-mediated effects on astrocytic tumor cell proliferation.

Neurotensin (NT) and neurotensin receptors (NTRs) are widely found in the brain, NT may be considered as a mitogen factor in some tissues. However, no NT-mediated effects on glioma cell proliferation have been reported so far. In our present study we investigated the influence of NT on the proliferation of astrocytic tumor cell lines. To this end we used a synthetic NT agonist (JMV-449), a protease inhibitor which blocks the natural degradation of NT (JMV-531), and NT. The in vitro biological models used in the present study included the low grade SW1088, and the high grade U87, U373 and A172 astrocytic tumor cell lines. The peptide-induced influence on astrocytic tumor cell proliferation was investigated by means of the colorimetric MTT assay. Our results show that the NT and the NT agonist significantly stimulated the proliferation in 2/4 and 3/4 of the astrocytic cell lines respectively. Similarly, compound JMV-531 also induced an increase in the proliferation of 2/4 of the astrocytic cell lines. This marked influence of the NT and NT agonists, or the enzyme-endogenous prevention of its degradation on the regulation of astrocytic tumor growth therefore suggests that NT antagonists might be used to treat certain patients with high grade astrocytic tumors that do not respond to chemotherapy and/or radiotherapy.

Astrocytoma↗

[Intra-cavernous collagen analysis in impotence].

The role of the different components of the corpus cavernosum is very important in the physiopathology of erectile dysfunction. The precise function of collagen fibers in erectile physiology is controversial. We measured the different types of collagen (I, III, IV) in the corpus cavernosum of 26 impotent and potent men using cell image analysis and immunohistochemistry. We found differences in the distribution of collagen I, III, IV in each pathological group (arterial, caverno-venous, psychogenic). The augmentation of collagen I and the light diminution in collagen III makes the corpus cavernosum less compliant which translates clinically as an alteration in the filling of the vascular spaces and by dysfunction of the veno-occlusive mechanism. The diminution in collagen IV shows an alteration in the function of endothelial cells. The fact that in the psychogenic group we found also a diminution in collagen IV content, makes us infer that psychogenic impotence could be the first stage of an organic impotence.

Adult↗

The contribution of image cytometry and artificial intelligence-related methods of numerical data analysis for adipose tumor histopathologic classification.

Thirty-five lipomatous tumors were quantitatively described using 47 variables generated by means of computer-assisted microscope analysis. Of these 47 quantitative variables, 27 were computed on Feulgen-stained specimens (25 on cytologic and 2 on histologic samples) and, of the remaining 20, 8 related to vimentin and S-100 protein immunostaining patterns and the other 12 to the glycohistochemical staining patterns of peanut agglutinin, succinylated wheat germ agglutinin, and concavalin A agglutinin. The 35 lipomatous tumors included 6 atypical lipomas and 8 well differentiated, 5 dedifferentiated, 6 myxoid, and 10 pleomorphic liposarcomas. The actual diagnostic value contributed by each of the 47 variables with respect to the 5 lipomatous tumor groups was determined by means of the decision tree technique, an artificial intelligence-related algorithm that forms part of the supervised learning algorithms. Of the 47 quantitative variables, the decision tree technique retained 8: i.e., 2 tissue architecture-, 2 DNA ploidy level-, 2 morphonuclear-, 1 lectin histochemical-, and 1 vimentin immunostain-related variables. The decision tree technique made use of these 8 variables to set up logical rules that make it possible to identify atypical lipomas from well differentiated liposarcomas, on the one hand, and dedifferentiated liposarcomas from those that are well differentiated and pleomorphic, on the other. Thus, the combination of an artificial intelligence algorithm analyzing quantitative variables generated by means of the computer-assisted microscope analysis of cytologic and histologic samples from lipomatous tumors can be considered an expert system contributing significant diagnostic information to conventional diagnosis.

Algorithms↗

Lectin histochemistry, ploidy level and proliferation indices in meningioma subtypes.

The glycohistochemical expression of binding sites for eight lectins is characterized in a series of 15 meningothelial, 10 fibroblastic and 15 transitional meningiomas. The correlation between lectin staining and either the proliferation index or ploidy level has also been investigated. The data show that the cytochemical binding of some lectins is of value in distinguishing between the different meningioma subgroups. For example, fibroblastic meningiomas express significantly higher amounts of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA-I) than the meningothelial sub-type. Diploid tumours express a higher glycine maximus (SBA), Arachis hypogaea (PNA) and Phaseolus vulgaris leukoagglutinin (PHA-L) binding than aneuploid tumours. These differences are probably due to the modification of post-transcriptional glycosylation events linked to tumour ageing. The data also reveal that the increased binding of PHA-L is inversely correlated with the proliferation indices of the tumours.

Histocytochemistry↗

Histochemical detection of expression of binding sites for labelled hyaluronic acid and carrier-immobilized synthetic (histo-blood group trisaccharides) or biochemically purified (ganglioside GM1) glycoligands in nasal polyps and other human lesions including neoplasms.

This study is intended to demonstrate the versatility and feasibility of custom-made oligosaccharide-exposing neoglycoconjugates including histo-blood group epitopes in various human lesions, including nasal polyps. The binding of the biotinylated probes was determined on formalin-fixed paraffin-embedded sections from archive materials. The general aspects of our results may be interpreted as follows: the neoglycoconjugates used here can readily detect differences in the ability of cells to bind glycan residues in tissue sections, thereby enabling the extent of the binding capacity of various types of human lesions to be compared. Furthermore, the reactivity to glycan may reflect characteristics of the cells and their environment. The investigation into pathological disorders with respect to the binding capacity of these carrier-immobilized mono- or oligosaccharide structures derived from custom-made synthesis or biochemical purification is based on the prospect of translating progress in this field into the establishment of potentially beneficial procedures for medical diagnosis and pathological classification.

Adenocarcinoma↗

The use of the digital cell image analysis of Feulgen-stained nuclei to detect apoptosis.

Cell death is an essential event in the functioning of multicellular organisms. It plays a role opposite to that of mitosis in the regulation of cell populations. In the present work, we describe an original methodology which permits the easy detection and count of apoptotic cells in a given tissue. This methodology is based on the digital cell image analysis of Feulgen-stained nuclei, which also permits the calculation of the proliferation index, i.e. the percentage of cells in the S phase of the cell cycle. This percentage of cells in the S phase is strongly related to the mitotic index. Our methodology, which involves the multivariate analysis of 14 morphonuclear parameters computed by means of the digitized cell image analysis of Feulgen-stained nuclei, was applied here to a well-known biological apoptosis model, namely glucocorticoid-treated rat thymocytes. The parameters that permitted the detection of apoptotic cells were the integrated optical density, a parameter that describes the nuclear DNA content, and the run length percentage and long run length parameters which are related to the pattern of chromatin condensation. This determination can be carried out on a relatively small number of cells.

Animals↗

Estrous cycle-related alterations in the expression of glycoconjugates and lectins in the mouse endometrium shown histochemically.

Alterations of the hormonal status may influence diverse cell features relevant to intra- and intercellular communication. We studied histochemically the expression of glycans and endogenous sugar-binding proteins (endolectins) in the mouse endometrium during the estrous cycle. The avidin-biotin-peroxidase complex (ABC) technique was used on paraffin sections with a panel of biotinylated lectins and neoglycoproteins. Stage-specific changes were observed with Galanthus nivalis agglutinin (GNA), Ulex europaeus-I agglutinin (UEA-1), Sambucus nigra agglutinin (SNA), Ricinus communis agglutinin (RCA-I) and Glycine max agglutinin (SBA) in both the luminal and the glandular epithelium, but to a lesser extent in the latter. The stromal constituents also exhibited modifications in lectin-binding profiles in cyclic mice. In addition to the analysis of cell glycans endogenous carbohydrate-binding sites were studied using synthetic probes, biotinylated neoglycoproteins. These tools made it possible to conclude that hormonal status can affect the expression of endolectins. We have attempted to correlate the glycohistochemical findings with recently published data obtained biochemically. The results indicate that phase-specific alterations in lectin-binding glycoproteins and endolectins occur in the endometrium of mice associated with their short reproductive cycle.

Animals↗

Perspectives in modern glycohistochemistry.

Owing to the biologic importance of glycans in many different settings, the author stresses favorable aspects of modern glycohistochemistry, a growing discipline in the field of glycobiology. The influence of the endocrine status on the expression of glycoconjugates in three targets: the mouse submandibular glands, the prostate and the endometrium is considered. The versatility of lectin and neoglycoprotein approaches is emphasized.

Androgens↗

Influence of culture media on the morphological differentiation of the PC-3 and DU145 prostatic neoplastic cell lines.

The concept of differentiation of prostate cancer in terms of morphonuclear characteristics and population dynamics was investigated on the PC-3 and DU145 cell lines. A software based on the concept of Voronoi paving was set up in order to characterize the structure of these cell lines growing in vitro on histological slides. The morphonuclear characteristics were assessed by means of the digital cell image analyses of Feulgen-stained nuclei. The in vitro "morphonuclear" and "pseudo-tissular" differentiations of the PC-3 and DU145 cells were described in terms of the use of various culture media, i.e., media supplemented with either 10% (F10 medium) or 1% (F1 medium) fetal calf serum and with (or without) platelet-derived growth factor and dihydrotestosterone (PA10 and PA1 media). The present data reveal that the PC-3 cell line would be more hormone-sensitive than the DU145 one. Indeed, decreasing the FCS concentration in the culture medium while adding DHT and PDGF led to marked modifications to the morphonuclear characteristics of the PC-3 cells, but not to the DU145 cells. These modifications corresponded to an increase in nuclear size occurring concomitantly with chromatin decondensation. In the same way, spectacular modifications in terms of medium-induced pseudo-tissular differentiation were observed in the PC-3 cell line, but not in the DU145 one. Such modifications corresponded to an increase in clone size related to an increase in the mean distances between neighboring cell nuclei in a given clone. Thus, according to the criteria defined in this study, the PC-3 cell line would seem to maintain a higher degree of differentiation than the DU145 cell line.

Animals↗

Characterization of the influence of anti-hormone and/or anti-growth factor neutralizing antibodies on cell clone architecture and the growth of human neoplastic astrocytic cell lines.

The influence of five anti-hormone and/or anti-growth factor neutralizing antibodies on the in vitro proliferation of four human astrocytic tumor cell lines (U87, U138, U373, H4) is quantitatively described by means of a new tool which makes it possible to evaluate cell growth and cell clone architecture concomitantly. This tool relies upon the combined use of the digital cell image analyses of Feulgen-stained nuclei and the Delaunay and Voronoi mathematical triangulation and paving techniques. Of the five anti-hormone and/or anti-growth factors tested here, the anti-luteinizing hormone-releasing hormone (LHRH) antibody induced the most marked perturbation in the U138 and U373 cell lines, whereas this role was played by the anti-epidermal growth factor (EGF) antibody in the U87 and H4 cell lines. The anti-gastrin (G) antibody significantly modified the growth and/or cell clone architecture of the U138, U87 and H4 cell lines, as did the anti-transforming growth factor alpha (TGFalpha) antibody. The anti-transforming growth factor beta (TGFbeta) antibody modified the growth and/or cell clone architecture of the four cell lines under study. If the five antibodies are taken into consideration, the results strongly suggest that four (the anti-G, the anti-EGF, the anti-LHRH and the anti-TGFalpha) act as inhibitory agents on some glioma cell line proliferation, while the fifth one, i.e. the anti-TGFbeta, act as a stimulator of cell proliferation, perhaps by abrogating the inhibitory effects of TGFbeta on proliferation. A comparison of cell growth data with cell clone architecture characteristics provided further evidence of some specific influence exercised by a given hormone and/or growth factor on glioma cell proliferation. Indeed, the anti-LHRH antibody caused the most pronounced perturbations in the U138 and U373 cell clone architecture; this feature was observed in the H4 cell line and, to a lesser extent in the U87 one after the anti-EGF antibody had been used.

Antibodies, Monoclonal↗