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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 199 records · Page 11Linked to original sources

Role of genomic instability in meningioma progression.

Microsatellite length instability, probably resulting from defective DNA mismatch repair mechanisms, has been described in a variety of cancers. Such genetic instability may play a significant role in tumor formation and progression. To investigate the role of microsatellite alterations in meningioma tumorigenesis and progression, we examined 33 microsatellite markers on nine chromosomes for abnormalities in 18 benign, 15 atypical, and 11 malignant meningiomas. In each tumor, at least 15 markers were investigated. Microsatellite instability was not detected in any of the cases examined. However, loss of heterozygosity for markers from various chromosomes was seen frequently among atypical and malignant meningiomas. Although some of these chromosomal losses might represent random events, our data also indicate a role for specific loci on chromosome arms 14q, 1p, 10q, and possibly 9p in the development of malignancy in meningiomas. Our results argue against a significant role for a generalized microsatellite instability phenotype in meningiomas, but they suggest that genomic instability resulting in frequent allelic deletions may contribute to meningioma progression.

Alleles↗

The impact of the Medicare Influenza Demonstration Project on influenza vaccination in a county in Massachusetts, 1988-1992.

Influenza and related pneumonia continue to cause significant amounts of morbidity and mortality despite the availability of effective vaccines. Two comparable counties in Massachusetts served as project areas of a national trial to see if reimbursement for immunizing Medicare-B eligible recipients against influenza would increase the use of the vaccine and reduce the costs attributed to related morbidity. Providers of health and social services to elders were recruited to participate in one county. A variety of professional and public education campaigns and media were used to promote influenza immunizations. Laboratory-based surveillance was instituted in both counties to assess the extent of circulating virus in each. Vaccine was made available to medical providers in both counties. While the amount of vaccine used in the comparison county increased by 6% from pre-project time (16,000 to 17,000 doses administered), vaccine use increased 219% in the intervention county (21,250 to 46,494 doses administered). In a post-project survey of participating physicians, 88% of 238 respondents reported administering less than 100 doses of influenza vaccine per year prior to the project. By the end of the project, only 32% administered less than 100 in the previous year. This project demonstrated the need for educating both the provider and the public in order to successfully promote immunizations. It was not clear, however, if reimbursement was a more important factor for promoting influenza immunizations than was universal distribution of free vaccine.

Aged↗

[Detection of clonality of cutaneous T-cell lymphomas using polymerase chain reaction].

Differentiation of a cutaneous lymphoma from a reactive lymphoid infiltrate is a demanding challenge for the pathologist. In this retrospective study we examined 24 paraffin-embedded tissue samples from lesions diagnosed as lymphomas and 7 control samples of skin affected by benign changes and with pronounced lymphoid infiltrates for clonal rearrangement of the gamma T-cell-receptor. Using PCR technology we demonstrated clonality in 22 cases of lymphoma (92%). Thus, the primer combination used in this study covering the four main groups (I-IV) of the variable region of the gamma T-cell receptor gene allows high sensitivity. No clonality was demonstrable in any of the 7 control cases. This study demonstrates the growing importance of PCR technology for the diagnosis of lymphoma.

Cell Transformation, Neoplastic↗

Ruminant cluster WC13.

Five monoclonal antibodies (mAbs) belonged to preliminary cluster 27; however, only two mAbs, Buf13 (3W-506) and Co-3D1D4 (3W-202), were shown to detect the same surface antigen and belong to WC13. The other three mAbs, IVA120 (3W-323), IVA197 (3W-533) and IVA198 (3W-290), detected a 45 kDa molecule that could be fibrinogen (Mateo A., Perez de la Lastra, J., Moreno, A., Dusinsky, R., Bilka, F., Simon, M., Horovska, L., Naessens, J. and Llanes, D., 1996. Biochemical characterization of antigens detected with anti-platelet monoclonal antibodies. Vet. Immunol. Immunopathol., 52: 363-370; Perez de la Lastra, J.M., Mateo, Dusinsky, R., Bilka, Simon, M., Horovska, L. and Llanes, D., 1996. Two monoclonal antibodies from the platelet panel recognize sheep plasma fibronigen. Vet. Immunol. Immunopathol., 52:).

Animals↗

Biochemical characterization of antigens detected with anti-platelet monoclonal antibodies.

A panel of 18 monoclonal antibodies (mAbs) defined by the third workshop as specific for platelets, clustered in three preliminary groups: PC7, PC13 and PC27. These mAbs were further analysed by immunoprecipitation using extracts of iodinated and biotinylated peripheral blood mononucleated cells (PBMC) and platelets. We could confirm the existence of mAbs with specificities to WC9 (in PC7) and CD41/61 (in PC13). Two mAbs formed a new cluster, WC13, which may be homologous to human CD31 (in PC27). The influence of EDTA and thrombin on the expression of the different antigens on the platelet membrane was assessed by flow cytometry (FCM) analysis, as well as cross-reactivity with platelets from different species.

Animals↗

Two monoclonal antibodies from the platelet panel recognize sheep plasma fibrinogen.

Among the monoclonal antibodies (mAbs) submitted to the third Workshop, two mAbs, IVA120 (3W-323) and IVA198 (3W-290), could be identified to recognize the sheep fibrinogen molecule. The apparent molecular weight of the immunoprecipitated 48-60 kDa cell surface protein under reducing conditions suggested this antigen could be the fibrinogen molecule. ELISA and immunoblotting assays, performed with commercially available sheep plasma fibrinogen, confirmed that these two mAbs recognize two different epitopes present on the sheep fibrinogen molecule.

Animals↗

Immunohistochemical reactivity of anti-platelet monoclonal antibodies.

Ten mAbs of preliminary clusters PC13 and PC27 with specificity for bovine platelets were studied by immunohistochemistry. Cryostat sections of bovine lymph node, spleen, thymus, small intestine, liver, kidney and smears of bone marrow cells were used. Five mAbs (CAPP2, IVA30, IVA125, IL-A164 and IL-A166) assigned to cluster PC13 (CD41/CD61) stained platelets and non-lymphocytic cells of various tissues. Our data confirm the presence of two specificities in PC27: three mAbs (IVA120, IVA197 and IVA198) specific for fibrinogen strongly reacted with the endothelial and reticular tissues whereas the other two mAbs Co-3D1D4 and Buf13 (WC13) were negative.

Animals↗

Repopulation of Langerhans cells during wound healing in an experimental human skin/SCID mouse model.

The epidermal repopulation of Langerhans cells (LCs) during wound healing was examined using a human skin severe combined immunodeficient (SCID) mouse model. The experiments, were carried out after proving the human origin of keratinocytes repopulating the wound beds using the W6/32 monoclonal antibody. It was shown that CD1a- and HLA-DR-positive dendritic cells (mostly LCs) are already detectable 2 days after injury within the newly formed epithelium. In the excisional wounds investigated, neither HLA-DR nor ICAM-1 expression of human keratinocytes was observed. Our present data suggest that LC repopulation is an early event in the process of re-epithelization.

Animals↗

Gaba-like immunoreactive terminals on lumbar motoneurons of the adult cat. A quantitative ultrastructural study.

The aim of this ultrastructural study was to analyse quantitatively the distribution of gamma-aminobutyric acid (GABA)-like immunoreactivity in axon terminals apposed to somatic and proximal dendritic membranes of cat motoneurons in lumbar column 2. Preembedding immunocytochemistry was used to count the GABAergic terminals contacting profiles of eighteen alpha-and six gamma-motoneurons. Of the 1293 terminals counted on the somatic and proximal dendritic compartments of alpha-motoneurons, 197 were GABAergic. In contrast, a total number of only 62 terminals were counted on gamma-motoneurons, of which 8 were GABAergic. These populations of GABAergic terminals were less numerous than the population of glycinergic terminals observed in a previous study. The morphometric characteristics of GABAergic synapses were analyzed using postembedding immunocytochemistry. Most of the GABAergic terminals contained pleomorphic vesicles (F-type boutons, flattened or pleomorphic vesicles). All terminals presynaptic (P boutons) to large terminals containing sphericle vesicles (M-type boutons, characteristic of alpha-motoneurons), were GABA-immunopositive. These results suggest that there are different distributions of the GABAergic control of excitability on gamma- and alpha-motoneurons. GABA appears to be strongly involved in post-synaptic inhibition of alpha-motoneurons, whereas gamma-motoneurons receive very few GABAergic inhibitory inputs. Morphological correlates of GABAergic presynaptic inhibition were seen on alpha- but not on gamma-motoneurons.

Animals↗

Postnatal development of alpha- and gamma-peroneal motoneurons in kittens: an ultrastructural study.

Motoneurons innervating the peroneus brevis muscle of 1 week- and 3 week-old kittens were retrogradely labelled by HRP and examined by electron microscopy. At 1 week the distribution of mean cell body diameters was unimodal. Consequently alpha- and gamma-motoneurons could not be identified by their size. The aim of this study was to see whether the alpha- and gamma-motoneurons of kittens could be identified using the combination of ultrastructural criteria previously defined in the adult cat. Using these three criteria it was not possible to distinguish all the motoneurons as either alpha- or gamma in the kitten and a fourth criterion (frequency of F bouton profiles) was added to aid identification. However, with these four criteria, at 1 week six of 21 motoneurons and at 3 weeks two of 18 could still not be clearly identified as alpha or gamma (four were tentatively considered to be gamma, and four could not be identified). The maturation of alpha-motoneurons between 1 week and the adult was accompanied by an increase in somatic membrane area and a significant decrease in the somatic packing density of F boutons. On gamma-motoneurons there was a decrease in the somatic packing density of F boutons between 1 and 3 weeks. However, the numbers of F and S boutons remained stable for both motoneuron types. Age-related changes in apposition and active zone lengths of F and S boutons characterize the synaptic rearrangements which are occurring during the postnatal development of motoneurons.

Age Factors↗

Persistent organochlorines in beluga whales (Delphinapterus leucas) from the St Lawrence River estuary--I. Concentrations and patterns of specific PCBs, chlorinated pesticides and polychlorinated dibenzo-p-dioxins and dibenzofurans.

Blubber samples from beluga whales (Delphinapterus leucas) in the St Lawrence River estuary were analysed for PCB congeners (ortho- and non-ortho-substituted) and other persistent organochlorines as well as chlorinated dibenzo-dioxins/furans (PCDD/Fs). Major individual components (mean concentrations > 1 microg g(-1)) were 4,4'-DDE, -DDD and -DDT, T12 (a toxaphene-related compound), trans-nonachlor, oxychlordane, mirex, HCB, tris(p-chlorophenyl) methane and dieldrin. Concentrations of SigmaPCBs (8.3-412 microg g(-1)), SigmaDDT (3.36-389 microg g(-1)) and mirex (0.18-6.8 microg g(-1)) were particularly elevated relative to other odontocetes in Canadian waters. SigmaDDT, PCBs (as Aroclor), mirex and T12 concentrations were positively correlated with age of adult females (> 10 years) but only weakly, or not significantly, correlated with age of adult males. PCDD/Fs were present at low ng kg(-1) levels and consisted mainly of penta- and hexachlorofurans, and hepta- and octachlorodioxin. CB126 (3,3',4,4',5-PCB) was the most prominent non-ortho-substituted PCB congener in beluga blubber. Total TCDD toxic equivalents averaged 330 ng kg(-1) in females and 1400 ng kg(-1) in males and were dominated by CB126, and the mono-ortho-substituted congeners CB105 and CB118. Biomagnification factors (BMFs) for mirex and SigmaPCB from fish to beluga ranged from 11 to 16, and were similar to BMFs in Arctic animals, indicating that elevated levels in St Lawrence animals are a consequence of relatively high levels of recalcitrant organochlorines in prey of the beluga in the St Lawrence river system.

Journal Article↗

Envoplakin, a novel precursor of the cornified envelope that has homology to desmoplakin.

The cornified envelope is a layer of transglutaminase cross-linked protein that is deposited under the plasma membrane of keratinocytes in the outermost layers of the epidermis. We present the sequence of one of the cornified envelope precursors, a protein with an apparent molecular mass of 210 kD. The 210-kD protein is translated from a 6.5-kb mRNA that is transcribed from a single copy gene. The mRNA was upregulated during suspension-induced terminal differentiation of cultured human keratinocytes. Like other envelope precursors, the 210-kD protein became insoluble in SDS and beta-mercaptoethanol on activation of transglutaminases in cultured keratinocytes. The protein was expressed in keratinizing and nonkeratinizing stratified squamous epithelia, but not in simple epithelia or nonepithelial cells. Immunofluorescence staining showed that in epidermal keratinocytes, both in vivo and in culture, the protein was upregulated during terminal differentiation and partially colocalized with desmosomal proteins. Immunogold EM confirmed the colocalization of the 210-kD protein and desmoplakin at desmosomes and on keratin filaments throughout the differentiated layers of the epidermis. Sequence analysis showed that the 210-kD protein is homologous to the keratin-binding proteins desmoplakin, bullous pemphigoid antigen 1, and plectin. These data suggest that the 210-kD protein may link the cornified envelope to desmosomes and keratin filaments. We propose that the 210-kD protein be named "envoplakin."

Amino Acid Sequence↗