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Phage-related surface modifications of Pseudomonas aeruginosa: effects on the biological activity of viable cells.

Lysogenic [EI(8)3] and phage 8-resistant mutant (EI/8S17) strains of Pseudomonas aeruginosa EI were isolated. Besides lacking the capacity to adsorb phage 8, strains EI(8)3 and EI/8s17 did not contain surface substrate for the depolymerase that is produced de novo when phage 8 infects wild-type strain. EI. The glycolipoprotein (GLP) in the wild type contains phage 8 receptors and surface substrate for the depolymerase, as well as possesses characteristics of a virulence factor; therefore, the chemical and biological characteristics of the derived strains were investigated. The neutral-sugar, amino sugar, and protein content of the GLPs from the derived strains differed quantitatively from that of the wild type. In spite of some cross-reactivity, the GLPs from all strains were antigenically distinct in the indirect hemagglutination inhibition test. In mice, the toxicity of the GLP from strain EI(8)3 equaled that of the wild type, but the GLP of strain EI/8s17 was threefold less toxic. Significantly fewer viable EI(8)3 cells were required for the mouse 50% lethal dose than for the cells of either the wild type or the phage-resistant mutant.

Antigens, Bacterial

Immobilization of neuraminidase and its potential application in the modification of cell surfaces.

Vibrio cholerae neuraminidase was immobilized on the inside of 1.0 mm inner diameter nylon tubing with retention of enzyme activity, when assayed at 37 degrees C and pH 5.5 with mucin as substrate. The stabilities of the immobilized and soluble enzymes were similar for up to 3 hr at 37 degrees C. Preliminary data indicated that immobilized neuraminidase will release sialic acid from the surface of leukemic AKR mouse thymus and spleen lymphocytes; however, the level of immobilized enzyme activity needs to be increased for practical applications. With this improvement immobilized neuraminidase could become a novel preparation for carrying out cell surface modifications with minimal enzyme contamination of the cell.

Animals

Modification of surface membrane antigens by trypsin.

Cultured 3T3 and PY-3T3 mouse fibroblasts were subjected to mild treatment with twice crystallized trypsin and their immunogenicity tested in ICR/CD-1 mice. Surface antigenic modifications were observed using the foot pad swelling assay for detection of delayed hypersensitive responses. Mice immunized with trypsin-treated 3T3 cells showed cell-mediated immune reactions following challenge with either homologous antigen or untreated PY-3T3 fibroblasts. In contrast, treatment of the virus-transformed cells with trypsin decreased their antigenicity as determined by this in vivo assay.

Animals

Surface chemical modification of hard tissues: I. Bone.

Surfaces of bone were modified in a controlled manner by grafting or by adding interpenetrating polymeric side chains to the bone substrate. The properties of the hard tissue surface attained varied widely. The surface alteration may improve the ability of hard tissues such as bone or dentin to adhere to restorative materials.

Acrylates

Modifications of lectin binding on human leukemic cells after neuraminidase treatment.

Cell surface modifications after vibrio cholerae neuraminidase treatment were investigated using three different tritiated lectins: Concanavalin A, Ricinus sanguineus agglutinin (R.S.A.) and Robinia pseudoacacia lectin. Lectin binding measurements were performed on untreated and enzyme treated cells. The cells used were from chronic and acute leukemic donors. After neuraminidase treatment, a significant increase in the number of receptor sites, from 1 to 3 times, was found in all cases tested and for all three lectins utilized with only one exception. The affinity constant was generally decreased after neuraminidase treatment. The increase in number lectin binding sites, indicating extensive modification of the cell surface, is completely consistant with the known importance of sialic acid in determining immunogenicity.

Binding Sites

Single antiplatelet therapy and tirofiban bridged with surface modified flow diverters for ruptured blood blister-like aneurysms: single center experience and systematic review.

BACKGROUND: Blood blister-like aneurysms (BBAs) of the internal carotid artery are rare but high risk lesions that frequently re-rupture due to their fragile structure and dissecting pathology. Treatment is particularly challenging in ruptured cases, given the risks associated with dual antiplatelet therapy. Recent advancements in flow diverter stents (FDSs) with surface modifications, and the use of single antiplatelet therapy (SAPT), offer a potential alternative strategy. METHODS: We conducted a retrospective review of 17 patients with ruptured internal carotid artery BBAs treated with surface modified FDS under SAPT (ticagrelor or prasugrel) bridged periprocedurally with intravenous tirofiban. All procedures were performed within the acute phase of subarachnoid hemorrhage. Clinical, radiographic outcomes, and procedure related complications were evaluated. RESULTS: Among 17 patients, 94.1% achieved complete angiographic occlusion, and 76.5% attained favorable clinical outcomes (modified Rankin Scale score ≤2). No aneurysm rebleeding or device related ischemic events occurred. A total of 11 patients underwent external ventricular drainage or ventriculoperitoneal shunting without discontinuing SAPT, and no hemorrhagic complications were observed. A literature review incorporating seven additional series identified a total of 42 FDS plus SAPT treated BBA cases, with similar safety and efficacy profiles. CONCLUSIONS: Surface modified FDS with SAPT and tirofiban bridging appears to be a promising treatment option for ruptured BBAs, offering high occlusion rates with minimal thromboembolic and hemorrhagic complications. Larger prospective studies are needed to validate these findings.

Humans

Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has emerged as a promising gene-editing platform for genetic disorders; however, its in vivo application remains limited by low delivery efficiency and biological barriers. Many CRISPR payloads fail to reach target sites due to extracellular degradation, immune clearance, and intracellular trafficking limitations. This review examines the interplay between biological barriers and nanoparticle engineering strategies for CRISPR/Cas9 delivery. A barrier-oriented engineering approach is proposed as a central framework, encompassing ligand-based surface modification for enhanced targeting and uptake, improved circulation stability via PEGylation and biomimetic coatings, and optimized payload release through endosomal escape strategies. Stimulus-responsive nanoparticle systems further enable spatiotemporal control over payload release. Nuclear targeting strategies, including optimization of nuclear localization signals (NLS) and exploitation of endogenous trafficking pathways, are highlighted as key factors for improving genome-level editing efficiency. Despite these advances, major challenges-including limited intracellular delivery efficiency, insufficient targeting precision, and safety concerns-continue to hinder clinical translation. Future directions highlight artificial intelligence-driven nanoparticle design, personalized delivery systems, and next-generation CRISPR platforms. Overall, an integrated, barrier-oriented engineering strategy is essential for advancing CRISPR/Cas9 delivery toward clinical applications, ultimately advancing global good health and well-being.

CRISPR/Cas9

Adaptive differences of the surface organization of horny cells.

The existence of a peculiar structural pattern of complementary villi and pores was observed on the squamous surfaces of palms and soles. These features, which might be considered as acquired and adaptive cell surface modifications, proved to be more conspicuous during a period of rat and human postnatal development.

Animals

The role of sialated glycoproteins in endocytosis, permeability and transmural passage in the myeloid endothelium.

Changes in the anionic charge distribution at the luminal face of the endothelium of the sinusoids of the bone marrow have been studied at sites of endocytosis by large bristle coated vesicles and at the sites of molecular permeability through diaphragmed fenestrae. The anionic charge distribution has also been studied at the abluminal aspect of these vessels at sites of transmural blood cell passage. Cationic surface markers such as colloidal iron, native ferritin and polycationic ferritin used at low pH, 1.8, and the use of neuraminidase show that the nonmodified endothelial cell surface has exposed sialic acid groups, which are absent at the sites of these functional specializations. Polycationic ferritin binding over a range of pH levels indicates the prsence of another species of anionic materials present at both the nonmodified cell surface and at the sites of the cell surface modifications. This second group of anionic compounds is neuraminidase resistant and has a pKa higher than that of sialic acid (pKa:2.6).

Binding Sites

An ultrastructural comparison of human endometrial adenocarcinoma with normal postmenopausal endometrium.

Although electron microscopy has been of limited value in detecting malignant neoplasms, some neoplasms do exhibit characteristic ultrastructural features. Intensive study of these features may offer insight into the etiology and activity of such tumors. In an attempt to characterize the ultrastructure of endometrial adenocarcinoma, tissue was examined with the electron microscope and compared with normal postmenopausal endometrium. Endometria from biopsy, hysterectomy, or curettage were processed routinely for light and electron microscopy. Several ultrastructural features of the adenocarcinoma were common both to previous descriptions of endometrium of the postovulatory phase and to the normal postmenopausal endometrium, described here, viz, atypical mitochondrial forms and cell surface modifications. Ribosomes were abundant in adenocarcinoma of the endometrium, normal postmenopausal endometrium, and normal cyclic endometrium in the preovulatory phase.

Adenocarcinoma

Effect of chemical modification of cell surface components of a brewer's yeast on the floc-forming ability.

Effects of treatments with proteolytic enzymes and protein-modifying reagents on flocculation of brewer's yeast IFO 2018 were investigated. The floc-forming ability of the yeast cells was irreversibly eliminated by treatment with papain, trypsin, chymotrypsin or pepsin, indicating that certain proteins on the cell surface participate in the yeast flocculation. Chemical modification with reagents, known to act on disulfide bridges, carboxyl and/or phosphate groups, phenolic groups, amino groups, and imidazole groups, also destroyed the ability to flocculate, although in some cases a high concentration (8 M) of urea was necessary in addition to protein-modifying reagents. Thus, it is suggested strongly that these functional groups of amino acid residues of the proteins are essential for the floc-forming ability of brewer's yeast cells.

Cell Wall

A comparative study of the effect of modification of the surface of human platelets on the receptors for aggregated immunoglobulins and for ristocentin-von Willebrand factor.

The receptors for aggregated immunoglobulin G (IgG) (an Fc receptor) and for ristocetin-von Willebrand factor on human platelets were studied by means of various modifications of the platelet surface. The expression of these receptors was measured by the agglutination of platelets to ristocetin in the presence of von Willebrand factor, which is part of the factor VIII complex, and by the binding of aggregated IgG coupled to 3H-labelled diazobenzene. Treatment of platelets with chymotrypsin, trypsin, papain and pronase which removed protein and glycoprotein from the platelet under conditions where the release reaction was inhibited caused loss of the expression of the receptor for ristocetin-von Willebrand factor and an enhancement of that for aggregated IgG. Induction of membrane changes with ADP and of the release reaction with the ionophore A23187 abolished agglutination to ristocentin-von Willebrand factor but did not alter the receptor for aggregated IgC. Possible contributions of unspecific membrane changes, produced by protease treatment of platelets, to the modification of receptor expression were eliminated by the use of formaldehyde-treated platelets. Trypsin, papain and pronase destroyed the ability of these platelets to agglutinate to ristocetin-von Willebrand factor but produced no change in the binding of aggregated IgC. Therefore, the receptor for ristocetin-von Willebrand factor is truly sensitive to proteolysis while the Fc receptor is not, but is partially masked by protease-sensitive material.

Adenosine Diphosphate

Chemical modification of the surfaces of bacterial cell walls.

The surfaces of the isolated cell walls of four bacterial species were studied by microelectrophoresis following chemical treatments intended to remove specific charged groups. Acid-base titrations of the walls were used to assess specificity and extent of the modifications. Carboxyl groups were specifically and completely modified by activation with a water-soluble carbodiimide and subsequent reaction with a nucleophile, such as glycinamide, to give an uncharged pH-stable product. Aqueous media and mild reaction conditions make the method suitable for modifying carboxyl groups on cell surfaces too labile to withstand the harsh conditions required for conventional esterification reactions. Use of the carbodiimide-mediated reaction for discharging carboxyl groups, along with fluorodinitrobenzene for discharging amino groups and extraction procedures for removing constituents carrying phosphoester groups (teichoic acids), made it possible to obtain information about the spatial arrangement of charged groups on the wall surfaces. Removal of the exterior negative charge dominating wall surfaces allowed underlying amino groups to become electrokinetically effective and, in the case of E. coli, also revealed a lipophilic region with an affinity for a cationic surfactant.

Bacillus

Elimination of Escherichia coli K88 adhesion determinant by antibody in porcine gut and mammary secretions following oral immunization.

1) Although virulence of enteropathogenic E. coli in the pig is essentially associated with the K88 adhesion determinant, protection of the neonate and weanling is not necessarily dependent upon antibodies to this surface antigen. 2) Modification of the surface antigenic characteristics of enteropathogens occurs in the presence of antibody, suggesting an immune mechanism of induced loss of the genetic elements responsible for the synthesis of K88. 3) Antibodies directed against the K88 antigen do not seem to participate in the elimination of the K88 antigen. These observations provide a new concept that antibody mediated mechanisms of host defense include elimination of virulence determinants, a feature vital to maintaining the balance of the host pathogen relationship favorable to the host.

Administration, Oral