Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib.

Multiple myeloma (MM) is a plasma cell malignancy localized in the bone marrow. Despite the introduction of novel therapies majority of MM patients relapse. We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy.

Biomechanical Evaluation of Custom Foot Orthoses for Hallux Valgus Deformity.

The purpose of the present study was to compare the hallux valgus deformity pressure parameters seen in standard footwear (no orthosis) versus the pressure observed in the same footwear with the addition of 3 different length orthoses. The forefoot pressure at a hallux valgus deformity was recorded with pressure sensors placed on the plantar, medial, and dorsal surface of the first metatarsal head. The participants performed walking trials without an orthosis and with orthoses of 3 different lengths.

Nonoperative management of retrocalcaneal pain with AFO and stretching regimen.

Background: Retrocalcaneal heel pain is caused by a spectrum of etiologies all resulting in the same symptom of pain at the tendon-Achilles insertion. Several studies have reported the outcomes of operative treatment, but none have reported the outcomes or success rates of nonoperative treatment. We describe a detailed treatment algorithm and report the clinical outcomes.

The bisecting GlcNAc in cell growth control and tumor progression.

The bisecting GlcNAc is transferred to the core mannose residue of complex or hybrid N-glycans on glycoproteins by the β1,4-N-acetylglucosaminyltransferase III (GlcNAcT-III) or MGAT3. The addition of the bisecting GlcNAc confers unique lectin recognition properties to N-glycans. Thus, LEC10 gain-of-function Chinese hamster ovary (CHO) cells selected for the acquisition of ricin resistance, carry N-glycans with a bisecting GlcNAc, which enhances the binding of the erythroagglutinin E-PHA, but reduces the binding of ricin and galectins-1, -3 and -8.

Extracorporeal shock wave treatment of non- or delayed union of proximal metatarsal fractures.

Background: Nonunion or delayed union of fractures in the proximal aspect of metatarsals 1 to 4 and Zone 2 of the fifth metatarsal were treated by high energy extracorporeal shock wave treatment (ESWT) to study the safety and efficacy of this method of treatment in a FDA study of the Ossatron device.

Materials And Methods: In a prospective single-arm, multi-center study, 34 fractures were treated in 32 patients (two subjects had two independent fractures) with ESWT. All fractures were at least 10 (range, 10 to 833) weeks after injury, with a median of 23 weeks.

Vaccination-induced IgG response to Galalpha1-3GalNAc glycan epitopes in lambs protected against Haemonchus contortus challenge infection.

Lambs vaccinated with Haemonchus contortus excretory/secretory (ES) glycoproteins in combination with the adjuvant Alhydrogel are protected against H. contortus challenge infection. Using glycan micro-array analysis we showed that serum from such vaccinated lambs contains IgG antibodies that recognise the glycan antigen Galalpha1-3GalNAc-R and GalNAcbeta1-4(Fucalpha1-3)GlcNAc-R.

Glycan microarray analysis of Candida glabrata adhesin ligand specificity.

The Candida glabrata genome encodes at least 23 members of the EPA (epithelial adhesin) family responsible for mediating adherence to host cells. To better understand the mechanism by which the Epa proteins contribute to pathogenesis, we have used glycan microarray analysis to characterize their carbohydrate-binding specificities. Using Saccharomyces cerevisiae strains surface-expressing the N-terminal ligand-binding domain of the Epa proteins, we found that the three Epa family members functionally identified as adhesins in Candida glabrata (Epa1, Epa6 and Epa7) bind to ligands containing a terminal galactose residue.

Chronic disease management: it's time for transformational change!

The authors of the lead essay present a compelling case for the development and implementation of a national strategy on chronic disease prevention and management (CDPM). The literature demonstrates that the Chronic Care Model can improve quality and reduce costs. Substantial evidence supports the role of health information technologies such as electronic health records (EHRs) in achieving these goals.

Identification of ligand specificities for glycan-binding proteins using glycan arrays.

Protein-glycan interactions mediate diverse biological processes in cell communication and innate immunity. They involve the binding of a protein on one cell surface to a glycosylated protein or lipid on an opposing cell surface. Understanding the functional significance of these interactions is of major interest to the scientific community.

A novel family of lectins evolutionarily related to class V chitinases: an example of neofunctionalization in legumes.

A lectin has been identified in black locust (Robinia pseudoacacia) bark that shares approximately 50% sequence identity with plant class V chitinases but is essentially devoid of chitinase activity. Specificity studies indicated that the black locust chitinase-related agglutinin (RobpsCRA) preferentially binds to high-mannose N-glycans comprising the proximal pentasaccharide core structure. Closely related orthologs of RobpsCRA could be identified in the legumes Glycine max, Medicago truncatula, and Lotus japonicus but in no other plant species, suggesting that this novel lectin family most probably evolved in an ancient legume species or possibly an earlier ancestor.

Specificity of DC-SIGN for mannose- and fucose-containing glycans.

The dendritic cell specific C-type lectin dendritic cell specific ICAM-3 grabbing non-integrin (DC-SIGN) binds to "self" glycan ligands found on human cells and to "foreign" glycans of bacterial or parasitic pathogens. Here, we investigated the binding properties of DC-SIGN to a large array of potential ligands in a glycan array format. Our data indicate that DC-SIGN binds with K(d)<2muM to a neoglycoconjugate in which Galbeta1-4(Fucalpha1-3)GlcNAc (Le(x)) trisaccharides are expressed multivalently.

Ipsilateral arthrodesis of the metatarsophalangeal and interphalangeal joints of the hallux.

Background: Arthrodesis of the metatarsophalangeal joint of the hallux is frequently used for treatment of a variety of disorders. However, occasionally patients who have complex deformities or degenerative changes of the hallux require reconstruction of both the metatarsophalangeal and interphalangeal joints. There is concern that arthrodesis of both the metatarsophalangeal and ipsilateral interphalangeal joints could be problematic, interfering with the toe-off phase of gait or with shoewear.

The liverwort Marchantia polymorpha expresses orthologs of the fungal Agaricus bisporus agglutinin family.

A lectin different from the previously described mannose-binding agglutinins has been isolated from the liverwort Marchantia polymorpha. Biochemical characterization of the purified lectin combined with the data from earlier transcriptome analyses demonstrated that the novel M. polymorpha agglutinin is not related to any of the known plant lectin families, but closely resembles the Agaricus bisporus-type lectins, which hitherto have been found exclusively in fungi.

Identification of the sialic acid structures recognized by minute virus of mice and the role of binding affinity in virulence adaptation.

Sialic acid binding is required for infectious cell surface receptor recognition by parvovirus minute virus of mice (MVM). We have utilized a glycan array consisting of approximately 180 different carbohydrate structures to identify the specific sialosides recognized by the prototype (MVMp) and immunosuppressive (MVMi) strains of MVM plus three virulent mutants of MVMp, MVMp-I362S, MVMp-K368R, and MVMp-I362S/K368R. All of the MVM capsids specifically bound to three structures with a terminal sialic acid-linked alpha2-3 to a common Galbeta1-4GlcNAc motif: Neu5Acalpha2-3Galbeta1-4GlcNAcbeta1-4Galbeta1-4GlcNAc (3'SiaLN-LN), Neu5Acalpha2-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAc (3'SiaLN-LN-LN), and Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)-GlcNAcbeta1-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3Galbeta1-4(Fucalpha1-3)GlcNAc (sLe(x)-Le(x)-Le(x)).

Role of the carbohydrate recognition domains of mouse galectin-4 in oligosaccharide binding and epitope recognition and expression of galectin-4 and galectin-6 in mouse cells and tissues.

Galectin-4 and its homologue galectin-6 are members of the tandem-repeat subfamily of monomer divalent galectins. Expression of mouse galectin-4 and galectin-6 by RT-PCR using primers designed to distinguish both galectin transcripts indicates that both are expressed in the small intestine, colon, liver, kidney, spleen and heart and P19X1 cells while only galectin-4 is expressed in BW-5147 and 3T3 cell lines. In situ hybridization confirmed the presence of galectin-4/-6 transcripts in the liver and small intestine.

Lectin from the Manila clam Ruditapes philippinarum is induced upon infection with the protozoan parasite Perkinsus olseni.

Glycan-binding proteins (lectins) are widely expressed in many invertebrates, although the biosynthesis and functions of the lectins are not well understood. Here we report that Manila clam (Ruditapes philippinarum) synthesizes a lectin termed Manila clam lectin (MCL) upon infection with the protozoan parasite Perkinsus olseni. MCL is synthesized in hemocytes as a approximately 74-kDa precursor and secreted into hemolymph where it is converted to 30- and 34-kDa polypeptides.

Biochemical and structural analysis of Helix pomatia agglutinin. A hexameric lectin with a novel fold.

Helix pomatia agglutinin (HPA) is a N-acetylgalactosamine (GalNAc) binding lectin found in the albumen gland of the roman snail. As a constituent of perivitelline fluid, HPA protects fertilized eggs from bacteria and is part of the innate immunity system of the snail. The peptide sequence deduced from gene cloning demonstrates that HPA belongs to a family of carbohydrate-binding proteins recently identified in several invertebrates.

Stage I and II posterior tibial tendon dysfunction treated by a structured nonoperative management protocol: an orthosis and exercise program.

Background: Posterior tibial tendon dysfunction (PTTD) is a relatively common problem of middle-aged adults that usually is treated operatively. The purpose of this study was to identify strength deficits with early stage PTTD and to assess the efficacy of a focused nonoperative treatment protocol.

Methods: Forty-seven consecutive patients with stage I or II posterior tibial tendon dysfunction were treated by a structured nonoperative protocol.

Versatile fluorescent derivatization of glycans for glycomic analysis.

The new field of functional glycomics encompasses information about both glycan structure and recognition by carbohydrate-binding proteins (CBPs) and is now being explored through glycan array technology. Glycan array construction, however, is limited by the complexity of efficiently generating derivatives of free, reducing glycans with primary amines for conjugation. Here we describe a straightforward method to derivatize glycans with 2,6-diaminopyridine (DAP) to generate fluorescently labeled glycans (glycan-DAP conjugates or GDAPs) that contain a primary amine for further conjugation.