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Biomedical subjects

E P Scheidegger

Publications and source records attributed to E P Scheidegger.

8 recordsLinked to original sources
PubMed2006

[Eosinophilia].

Eosinophils normally account for only one to three percent of peripheral-blood leukocytes, and the upper limit of the normal range is 450 cells per cubic millimeter of blood. Eosinophilia occurs in a variety of disorders. The most common cause of eosinophilia worldwide is helminthic infections, and the most common cause in industrialized nations is atopic disease. The diverse causes, clinical signs and symptoms, the diagnostic work-up as well as the therapeutic strategies will be discussed in this review. The "hypereosinophilic syndrome" constitutes an evolving concept and is most likely the result of a clonal (neoplastic) disorder. A number of new therapeutic approaches for these conditions have been developed and will be discussed in this article.

Eosinophilia↗
PubMed2001

Fuc-TVII is required for T helper 1 and T cytotoxic 1 lymphocyte selectin ligand expression and recruitment in inflammation, and together with Fuc-TIV regulates naive T cell trafficking to lymph nodes.

To determine how the alpha(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the selectin ligands they control may contribute to the adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient in either or both enzymes. We find a substantial CHS deficiency in Fuc-TVII(-/-) mice, and a complete deficiency in Fuc-TIV(-/-)/Fuc-TVII(-/-) mice. These defects are not accounted for by alterations in the number or function of epidermal Langerhans cells required for cutaneous antigen processing and presentation. By contrast, defective CHS in Fuc-TVII(-/-) mice or Fuc-TIV(-/-)/Fuc-TVII(-/-) mice is attributed in part to prominent, or nearly complete deficiencies, respectively, in the complement of naive T lymphocytes available in lymph nodes for antigen-dependent activation, expansion, differentiation, and dissemination. Fuc-TVII deficiency also deletes expression of E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous sites in vivo, and thereby controls an essential component of the efferent phase of the cutaneous immune response. These observations indicate that collaborative contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to lymphocyte recruitment, are requisite components of the primary cellular immune response, and assign an essential role to Fuc-TVII in control of E- and P-selectin ligand expression by Th1 and Tc1 lymphocytes.

Animals↗
PubMed2000

Multifocal fixed drug eruption to paracetamol, tropisetron and ondansetron induced by interleukin 2.

Fixed drug eruptions (FDEs) represent an uncommon subset of drug reactions where typically dusky red skin eruptions recur at the same site each time a drug is administered. Multifocal FDEs are defined by skin eruptions at more than one site. We describe a patient with metastatic melanoma who developed a multifocal FDE to paracetamol, tropisetron and ondansetron during chemoimmunotherapy with interleukin 2 (IL-2) and dacarbazine. This case is unique since to our knowledge there has been no previous report of such a drug reaction to tropisetron. Moreover, recurrences were induced by drugs which were chemically unrelated (i.e. tropisetron and paracetamol). We propose that this unusual skin reaction to multiple drugs was induced by IL-2 administered during immunochemotherapy for the metastatic melanoma.

Acetaminophen↗
PubMed1999

Periarteritis nodosa presenting as a breast lesion: report of a case and review of the literature.

We describe a 34-year-old woman with periarteritis nodosa (PAN) presenting as a breast lesion. Localized involvement of the breast is an unusual manifestation of PAN. To date, 10 cases have been reported: all were in women with an age range of 45-78 years (mean 63). In most cases, breast lesions were an isolated finding, and the prognosis was favourable, setting them apart from the more common form of systemic PAN. The case presented is unusual in that vasculitis developed in the postpartum period, and was associated with cutaneous PAN-like lesions elsewhere on the body, and digital artery occlusion. The most important differential diagnoses of PAN of the breast are infectious mastitis, mammary malignancy and other forms of idiopathic vasculitides of the breast, e.g. giant cell arteritis and Wegener granulomatosis.

Adult↗
PubMed1996

Expression of the alpha(1,3)fucosyltransferase Fuc-TVII in lymphoid aggregate high endothelial venules correlates with expression of L-selectin ligands.

Lymphocyte homing to lymph nodes and Peyer's patches is mediated, in part, by adhesive interactions between L-selectin expressed by lymphocytes and L-selectin ligands displayed at the surface of the cuboidal endothelial cells lining the post-capillary venules within lymphoid aggregates. Candidate terminal oligosaccharide structures thought to be essential for effective L-selectin ligand activity include a sulfated derivative of the sialyl Lewis x tetrasaccharide. Cell type-specific synthesis of this oligosaccharide is presumed to require one or more alpha(1,3)fucosyltransferases, operating upon common 3'-sialylated and/or sulfated N-acetyllactosamine-type precursors. The identity of the alpha(1,3)fucosyltransferase(s) expressed in cells that bear L-selectin ligands has not been defined. We report here the molecular cloning and characterization of a murine alpha(1,3)fucosyltransferase locus whose expression pattern correlates with expression of high affinity ligands for L-selectin. In situ hybridization and immunohistochemical analyses demonstrate that this cDNA and its cognate alpha(1,3)fucosyltransferase are expressed in endothelial cells lining the high endothelial venules of peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. These expression patterns correlate precisely with the expression pattern of L-selectin ligands identified with a chimeric L-selectin/IgM immunohistochemical probe and by the high endothelial venule-reactive monoclonal antibody MECA-79. Transcripts corresponding to this cDNA are also detected in isolated bone marrow cells, a source rich in the surface-localized ligands for E- and P-selectins. Sequence and functional analyses indicate that this murine enzyme corresponds to the human Fuc-TVII locus. These observations suggest that Fuc-TVII participates in the generation of alpha(1,3)fucosylated ligands for L-selectin and provide further evidence for a role for this enzyme in E- and P-selectin ligand expression in leukocytes.

Amino Acid Sequence↗
PubMed1995

A human STX cDNA confers polysialic acid expression in mammalian cells.

Polysialic acid, or PSA, is a term used to refer to linear homopolymers of alpha(2,8)-sialic acid residues displayed at the surface of some mammalian cells. PSA is typically linked to the neural cell adhesion molecule N-CAM, where it can modulate the homotypic adhesive properties of this polypeptide. PSA expression is developmentally regulated, presumably through mechanisms involving regulated expression of sialyltransferases involved in PSA biosynthesis. Several different sialytransferase sequences have been implicated in PSA expression, although the precise roles of these enzymes in this context remain unclear. One such sequence, termed STX, maintains approximately 59% amino acid sequence identity with another sialyltransferase (PST-1, from hamster; PST, human) that is known to participate in PSA expression. While a murine STX fusion protein can catalyze the synthesis of a single alpha(2,8)-sialic acid linkage in vitro, the ability of STX to participate in PSA expression in vivo has not been demonstrated. We show here that STX transcripts are present in a PSA-positive, N-CAM-positive human small cell carcinoma line (NCI-H69/F3), but are absent in a variant of this line (NCI-H69/E2) selected to be PSA-negative and N-CAM-positive. To functionally confirm this correlation, we have cloned a human cDNA encoding the human STX sequence, and show, by transfection studies, that human STX can restore PSA expression when expressed in the PSA-negative, N-CAM-positive small cell carcinoma variant. We furthermore show that STX can confer PSA expression when expressed in a PSA-negative, N-CAM-positive murine cell line (NIH-3T3 cells), or when expressed in PSA-negative, N-CAM-negative COS-7 cells. These observations imply that STX, like PST-1/PST, can determine PSA expression in vivo. When considered together with the correlation between STX expression and PSA expression in vivo in the brain, these results suggest a regulatory role for STX in PSA expression in the developing central nervous system and small cell lung carcinoma.

3T3 Cells↗
PubMed1994

In vitro and in vivo growth of clonal sublines of human small cell lung carcinoma is modulated by polysialic acid of the neural cell adhesion molecule.

BACKGROUND: Polysialic acid (poly Sia) of the neural cell adhesion molecule (N-CAM) is an oncodevelopmental antigen and is found in small cell lung carcinomas (SCLC) as well as cell lines derived from these tumors. EXPERIMENTAL DESIGN: Cell heterogeneity in poly Sia expression was observed in primary SCLC and cell cultures of SCLC by immunostaining using a directly gold-labeled monoclonal antibody against poly Sia (MAb 735) and antibodies against N-CAM. Clonal sublines of the N-CAM-positive SCLC cell line, NCI-H69 were established to study the basis of this heterogeneity. The resulting sublines were examined for the proportion of cells expressing poly Sia, the stability of poly Sia expression, and the possible involvement of DNA methylation. Two of the sublines that expressed poly Sia on 0 and 95% of the cells were used in three independent in vitro assays to investigate the importance of poly Sia in cell-cell aggregation, disaggregation and cell to substrate adherence. Finally, clonogenic growth of these sublines was studied in soft agar and in the nude mouse. RESULTS: The proportion of cells immunoreactive for poly Sia was stable in serial subculture in these clones and was not affected by reducing DNA methylation. In aggregation and disaggregation assays, poly Sia was shown to modulate both calcium-dependent and independent cell-cell adhesion. No measurable differences in the attachment rates to various substrates (collagen type IV, laminin, heparan sulfate, and poly-L-lysine) were detected between the sublines. Cells from the poly Sia-positive clonal subline formed significantly more colonies in semisolid media and more intracutaneous metastasis in the nude mouse. CONCLUSIONS: Poly Sia does not occur on all N-CAM immunoreactive cells of SCLC. Poly Sia on SCLC cells is a clonable trait and high poly Sia expression correlates with reduced cell-cell adherence, a greater clonogenic ability in semisolid media, and a significantly higher incidence of intracutaneous metastases in nude mice.

Animals↗