The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing.

E-, P-, and L-selectin counterreceptor activities, leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by alpha(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in leukocyte recruitment is contradictory and incomplete. We show here that inflammation-dependent leukocyte recruitment retained in FucT-VII deficiency is extinguished in FucT-IV(-/-)/FucT-VII(-/-) mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII(-/-) mice is revoked in FucT-IV(-/-)/FucT-VII(-/-) mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of leukocyte recruitment and lymphocyte homing.

Squamous cell carcinoma of the buccal mucosa.

The purpose of this study was to establish treatment criteria for patients with early-stage squamous cell carcinoma of the buccal mucosa. Thirty-one patients were analyzed in a retrospective fashion. Distribution of patients according to tumor stage was relatively even. Within 5 years recurrent disease developed in nearly 80% of evaluable patients. There was a 100% overall incidence of local disease recurrence for patients with stage I and II tumors treated with wide local excision alone and followed up for more than 2 years. On the basis of these data, we conclude that wide local excision for early-stage buccal carcinoma is associated with a high local failure rate. Possible causes for failure and alternative treatment approaches are discussed.

The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis.

alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte counterreceptors for E- and P-selectins and of L-selectin ligands expressed by lymph node high endothelial venules (HEV). The identity of the alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain, as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand activity. We demonstrate here that mice deficient in alpha(1,3) fucosyltransferase Fuc-TVII exhibit a leukocyte adhesion deficiency characterized by absent leukocyte E- and P-selectin ligand activity and deficient HEV L-selectin ligand activity. Selectin ligand deficiency is distinguished by blood leukocytosis, impaired leukocyte extravasation in inflammation, and faulty lymphocyte homing. These observations demonstrate an essential role for Fuc-TVII in E-, P-, and L-selectin ligand biosynthesis and imply that this locus can control leukocyte trafficking in health and disease.

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.

Molecular cloning, expression, chromosomal assignment, and tissue-specific expression of a murine alpha-(1,3)-fucosyltransferase locus corresponding to the human ELAM-1 ligand fucosyl transferase.

Terminal Fuc alpha 1-3GlcNAc moieties are displayed by mammalian cell surface glycoconjugates in a tissue-specific manner. These oligosaccharides participate in selectin-dependent leukocyte adhesion and have been implicated in adhesive events during murine embryogenesis. Other functions for these molecules remain to be defined, as do the tissue-specific expression patterns of the corresponding alpha-(1-3)-fucosyltransferase (alpha 1-3FT) genes. This report characterizes a murine alpha 1-3FT that shares 77% amino acid sequence identity with human ELAM ligand fucosyltransferase (ELFT, also termed Fuc-TIV). The corresponding gene maps to mouse chromosome 9 in a region of homology with the Fuc-TIV locus on human chromosome 11q. In vitro, the murine alpha 1-3FT can efficiently fucosylate the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc (apparent Km of 0.71 mM) to form an unusual tetrasaccharide (Gal alpha 1-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc) described in periimplantation mouse tissues. The enzyme can also form the Lewis x determinant from Gal beta 1-4GlcNAc (Km = 2.05 mM), and the sialyl Lewis x determinant from NeuNAc alpha 2-3Gal beta 1-4GlcNAc (Km = 1.78mM). However, it does not yield sialyl Lewis x determinants when expressed in a mammalian cell line that maintains sialyl Lewis x precursors. Transcripts from this gene accumulate to low levels in hematopoietic organs, but are unexpectedly abundant in epithelia that line the stomach, small intestine, colon, and epididymus. Epithelial cell-specific expression of this gene suggests function(s) in addition to, and distinct from, its proposed role in selectin ligand synthesis.

Molecular cloning of a cDNA encoding a novel human leukocyte alpha-1,3-fucosyltransferase capable of synthesizing the sialyl Lewis x determinant.

The sialyl Lewis x determinant (NeuAc alpha 2,3Gal beta 1, 4[Fuc alpha 1,3]GlcNAc) is an essential component of leukocyte counterreceptors for E-selectin and P-selectin. The final step in sialyl Lewis x synthesis is catalyzed by alpha-1,3-fucosyltransferases acting on sialylated glycoconjugate precursors. Cultured human leukocytic cell lines express an alpha-1,3-fucosyltransferase gene termed Fuc-TIV or ELFT but do not express the other three cloned human alpha-1,3-fucosyltransferase genes to any significant degree. The physiological role of Fuc-TIV/ELFT in sialyl Lewis x biosynthesis is uncertain, however, since it can catalyze the synthesis of this determinant in some, but not all, transfected cell lines in a manner that is dependent upon the glycosylation phenotype of the host cell. We report here the molecular cloning of a cDNA encoding a new human leukocyte alpha-1,3-fucosyltransferase, termed Fuc-TVII, capable of synthesizing the sialyl Lewis x moiety. The cDNA sequence predicts a 341-amino acid-long type II transmembrane protein typical of mammalian glycosyltransferases. When expressed in mammalian cells, the Fuc-TVII cDNA directs the synthesis of cell surface sialyl Lewis x moieties but not the Lewis x, Lewis a, sialyl Lewis a, or VIM-2 determinants. Fuc-TVII can efficiently utilize alpha-2,3-sialyllactosamine in vitro to form the sialyl Lewis x tetrasaccharide but does not utilize lactosamine to form the Lewis x moiety. Northern blot analyses show that the Fuc-TVII gene is transcribed in HL-60 cells, a human promyelocytic cell line, and in YT cells, a natural killer-like cell line. Fuc-TVII represents a leukocytic alpha-1,3-fucosyltransferase that can participate in selectin ligand synthesis via its ability to catalyze the synthesis of sialyl Lewis x determinants.

Computed tomography of abdominal aortic aneurysm. An in vivo pathological report with a note on dynamic predictors.

A group of computed tomography (CT) descriptors were derived for abdominal aortic aneurysms. Terminology was defined and applied to the interpretation of the CT image in 55 prospective cases. Correlation of geometric parameters of aneurysm and analysis of the relationship of internal aneurysm components such as lumen and thrombus was performed. Predictive growth patterns for aneurysm demonstrated a synchronous increase in the volume of thrombus within the aneurysm in those aneurysms measuring 5 to 7 cm. Aneurysms greater than 7 cm were associated with an expansion of the patent pulsatile lumen, with no appreciable increase in thrombus volume. The thrombus-lumen ratio effectively described the changing internal architecture of aneurysm associated with increase in size. Proper utilization of CT descriptors develops a language that interprets aneurysm stability and potential for rupture and may provide an improved basis for timely surgical planning.

Lower extremity swelling: computerized tomography following negative venography.

In 21 patients who had lower extremity swelling and negative venography, radiographic evaluation was extended to include computerized tomography (CT) of the lower extremity, which we have termed venography-CT, or VCT. All patients were referred with the diagnosis of deep vein thrombosis (DVT) and no patient had a history of trauma. CT was effective in demonstrating two occult mechanisms of lower extremity swelling: knee joint effusion (three patients) and intramuscular hemorrhage (five patients). Selective utilization of CT in the evaluation of lower extremity swelling is effective in directing the clinical management of these patients.

Oblique hilar tomography, computed tomography, and mediastinoscopy for prethoracotomy staging of bronchogenic carcinoma.

Preoperative oblique hilar tomography was used to evaluate hilar lymph nodes in 150 patients with clinically resectable bronchogenic carcinoma. CT was also used in the evaluation of mediastinal lymph nodes in 50 of these patients. Subsequently, all patients underwent mediastinoscopy and/or thoracotomy. Hilar and mediastinal nodes were evaluated for the presence of metastasis, and these findings were then correlated with the radiographic findings of oblique hilar tomography and CT. CT was found to be a reliable method for prethoracotomy staging of bronchogenic carcinoma and for selecting patients for mediastinoscopy. The sensitivity of CT for evaluation of mediastinal nodal metastasis was 83% and the specificity was 90%. Thus patients with negative mediastinal CT need not undergo mediastinoscopy prior to thoracotomy, while mediastinoscopy and biopsy should be done in patients with enlarged mediastinal nodes on CT. Oblique hilar tomography is an accurate method for evaluation of hilar adenopathy and for predicting mediastinal involvement by extrapolation.

[The role of mathematical models in microhemorheology (author's transl)]. / Die Rolle mathematischer Modelle in der Mikrohämorheologie.

The basic fluid-mechanical and structural elements that determine the microhemorheological behavior of blood are presented and discussed. Microhemorheological models are classified into three groups: empirical models, theoretical models, and hybrid models. Major contributions in each area are reviewed and the state-of-the-art in microhemorheological modelling is discussed. Finally, important areas of future research are delineated.