Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscle development in vivo involves a complex sequence of cell-cell interactions in which secondary myotubes first form in association with primary myotubes and subsequently separate from them. We show here that during this process N-cadherin and the different structural forms of NCAM are regulated in a pattern that involves both temporal changes in expression and localization to particular regions of the muscle cell surface. In particular, levels of N-cadherin on maturing myotubes are decreased, and the form of NCAM synthesized by the muscle changes from a transmembrane non-polysialylated to a lipid-linked polysialylated membrane protein. Moreover, while NCAM was distributed on all myotube surfaces, the polysialyated form of NCAM was restricted to regions of the myotube surface that had recently separated from neighboring cells. We previously found that blockade of nerve-induced activity by d-Tubocurarine perturbed muscle cell interactions, resulting in a failure of myotubes to separate. We now show that this activity blockade also alters adhesion molecule expression. First, N-cadherin was no longer down-regulated in maturing myotubes, and its persistence on the surfaces of mature myotubes may partly explain their failure to separate. Secondly, the developmental switch from transmembrane to lipid-linked NCAM did not occur, and polysialylated NCAM was no longer formed. As the unusual physical properties of PSA have been proposed to impede cell-cell interactions, this alteration would also be expected to compromise cell separation. Together, these results suggest that the regulated expression of both N-cadherin and NCAM isoforms including their polysialylation, is an essential mechanism for the normal separation of secondary myotubes from primary myotubes.
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PMID:Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic acid on chick myotubes during development. 827 4

New gene expressed in prostate (NGEP) is a prostate-specific gene encoding either a small cytoplasmic protein (NGEP-S) or a larger polytopic membrane protein (NGEP-L). NGEP-L expression is detectable only in prostate cancer, benign prostatic hyperplasia and normal prostate. We have identified an HLA-A2 binding NGEP epitope (designated P703) which was used to generate T cell lines from several patients with localized and metastatic prostate cancer. These T cell lines were able to specifically lyse HLA-A2 and NGEP-expressing human tumor cells. NGEP-P703 tetramer binding assays demonstrated that metastatic prostate cancer patients had a higher frequency of NGEP-specific T cells when compared with healthy donors. Moreover, an increased frequency of NGEP-specific T cells was detected in the peripheral blood mononuclear cells of prostate cancer patients post-vaccination with a PSA-based vaccine, further indicating the immunogenicity of NGEP. These studies thus identify NGEP as a potential target for T cell-mediated immunotherapy of prostate cancer.
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PMID:New gene expressed in prostate: a potential target for T cell-mediated prostate cancer immunotherapy. 1949 50

Detergents are essential tools for membrane protein manipulation. Micelles formed by detergent molecules have the ability to encapsulate the hydrophobic domains of membrane proteins. The resulting protein-detergent complexes (PDCs) are compatible with the polar environments of aqueous media, making structural and functional analysis feasible. Although a number of novel agents have been developed to overcome the limitations of conventional detergents, most have traditional head groups such as glucoside or maltoside. In this study, we introduce a class of amphiphiles, the PSA/Es with a novel highly branched pentasaccharide hydrophilic group. The PSA/Es conferred markedly increased stability to a diverse range of membrane proteins compared to conventional detergents, indicating a positive role for the new hydrophilic group in maintaining the native protein integrity. In addition, PDCs formed by PSA/Es were smaller and more suitable for electron microscopic analysis than those formed by DDM, indicating that the new agents have significant potential for the structure-function studies of membrane proteins.
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PMID:Highly Branched Pentasaccharide-Bearing Amphiphiles for Membrane Protein Studies. 2696 56

(68)Gallium (Ga)-PSMA PET/CT (PSMA stands for "prostate-specific membrane antigen") is a new diagnostic tool for patients with prostate cancer or with prostate cancer metastases. PET/CT is a combination scan which uses the physiological information of the PET scan and the anatomic information of the CT scan. The radioligand (68)Ga-PSMA is a radioactively labelled peptide that binds to the membrane protein PSMA. Prostate cancer cells in the primary tumour and in metastases express increased levels of PSMA in the plasma membrane. A number of studies have shown that (68)Ga-PSMA PET/CT is sensitive in detecting primary prostate cancer and metastases in lymph nodes and bone. In the same patient, (68)Ga-PSMA PET/CT detects more metastases in an earlier phase, i.e. at a lower PSA level, than fluorine-18 choline PET/CT. Furthermore, the (68)Ga-PSMA can be produced in the investigating hospital with a gallium generator. The expectation is that the use of (68)Ga-PSMA PET/CT will increase to a major extent over the coming years in patients with prostate cancer.
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PMID:[Not Available]. 2714 5

Glycoconjugate vaccines use protein carriers to improve the immune response to polysaccharide antigens. The protein component allows the vaccine to interact with T cells, providing a stronger and longer-lasting immune response than a polysaccharide interacting with B cells alone. Whilst in theory the mere presence of a protein component in a vaccine should be sufficient to improve vaccine efficacy, the extent of improvement varies. In the present review, a comparison of the performances of vaccines developed with and without a protein carrier are presented. The usefulness of analytical tools for macromolecular integrity assays, in particular nuclear magnetic resonance, circular dichroism, analytical ultracentrifugation and SEC coupled to multi-angle light scattering (MALS) is indicated. Although we focus mainly on bacterial capsular polysaccharide-protein vaccines, some consideration is also given to research on experimental cancer vaccines using zwitterionic polysaccharides which, unusually for polysaccharides, are able to invoke T-cell responses and have been used in the development of potential all-polysaccharide-based cancer vaccines.A general trend of improved immunogenicity for glycoconjugate vaccines is described. Since the immunogenicity of a vaccine will also depend on carrier protein type and the way in which it has been linked to polysaccharide, the effects of different carrier proteins and production methods are also reviewed. We suggest that, in general, there is no single best carrier for use in glycoconjugate vaccines. This indicates that the choice of carrier protein is optimally made on a case-by-case basis, based on what generates the best immune response and can be produced safely in each individual case.Abbreviations: AUC: analytical ultracentrifugation; BSA: bovine serum albumin; CD: circular dichroism spectroscopy; CPS: capsular polysaccharide; CRM197: Cross Reactive Material 197; DT: diphtheria toxoid; Hib: Haemophilius influenzae type b; MALS: multi-angle light scattering; Men: Neisseria menigitidis; MHC-II: major histocompatibility complex class II; NMR: nuclear magnetic resonance spectroscopy; OMP: outer membrane protein; PRP: polyribosyl ribitol phosphate; PSA: Polysaccharide A1; Sa: Salmonella; St.: Streptococcus; SEC: size exclusion chromatography; Sta: Staphylococcus; TT: tetanus toxoid; ZPS: zwitterionic polysaccharide(s).
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PMID:Glycoconjugate vaccines: some observations on carrier and production methods. 3204 49