CD4 Immunoadhesins: Chimeric molecules resulting from the fusion of recombinant soluble CD4 to the Fc portion of immunoglobulins. These have potential use in the therapy of AIDS since they possess both the gp120-binding and HIV-blocking properties of rCD4 as well as the long plasma half-life and Fc receptor-binding functions of immunoglobulin.Antigens, CD8: Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Antigens, CD40: A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Antigens, CD44: Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Antigens, CD28: Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.CD4-CD8 Ratio: Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.Antigens, CD14: Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.Antigens, CD38: A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Antigens, CD1: Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.Antigens, CD80: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Antigens, CD2: Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.Nucleosides: Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)HIV Envelope Protein gp120: External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.HIV Envelope Protein gp160: An envelope protein of the human immunodeficiency virus that is encoded by the HIV env gene. It has a molecular weight of 160,000 kDa and contains numerous glycosylation sites. It serves as a precursor for both the HIV ENVELOPE PROTEIN GP120 and the HIV ENVELOPE PROTEIN GP41.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Intellectual Property: Property, such as patents, trademarks, and copyright, that results from creative effort. The Patent and Copyright Clause (Art. 1, Sec. 8, cl. 8) of the United States Constitution provides for promoting the progress of science and useful arts by securing for limited times to authors and inventors, the exclusive right to their respective writings and discoveries. (From Black's Law Dictionary, 5th ed, p1014)Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Membrane Fusion: The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Single-Chain Antibodies: A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Abbreviations as Topic: Shortened forms of written words or phrases used for brevity.Immunoglobulins, Intravenous: Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.Immunization, Passive: Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Cytomegalovirus Infections: Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults.Cytomegalovirus: A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.Body Composition: The relative amounts of various components in the body, such as percentage of body fat.Absorptiometry, Photon: A noninvasive method for assessing BODY COMPOSITION. It is based on the differential absorption of X-RAYS (or GAMMA RAYS) by different tissues such as bone, fat and other soft tissues. The source of (X-ray or gamma-ray) photon beam is generated either from radioisotopes such as GADOLINIUM 153, IODINE 125, or Americanium 241 which emit GAMMA RAYS in the appropriate range; or from an X-ray tube which produces X-RAYS in the desired range. It is primarily used for quantitating BONE MINERAL CONTENT, especially for the diagnosis of OSTEOPOROSIS, and also in measuring BONE MINERALIZATION.Muscle Strength: The amount of force generated by MUSCLE CONTRACTION. Muscle strength can be measured during isometric, isotonic, or isokinetic contraction, either manually or using a device such as a MUSCLE STRENGTH DYNAMOMETER.Bone Resorption: Bone loss due to osteoclastic activity.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Heterocyclic Compounds, Bridged-Ring: A class of organic compounds which contain two rings that share a pair of bridgehead carbon atoms.Cytopathogenic Effect, Viral: Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses.Cell Line: Established cell cultures that have the potential to propagate indefinitely.HIV Seropositivity: Development of neutralizing antibodies in individuals who have been exposed to the human immunodeficiency virus (HIV/HTLV-III/LAV).Cell Line, Tumor: A cell line derived from cultured tumor cells.Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.

The relationship between pityriasis rubra pilaris and inflammatory arthritis: case report and response of the arthritis to anti-tumor necrosis factor immunotherapy. (1/19)

Pityriasis rubra pilaris (PRP) refers to a group of erythematous, scaling dermatologic conditions that have been associated with seronegative arthritis. We report a case of polyarthritis in a young man with PRP in which magnetic resonance imaging suggested an entheseal-based pathology for the joint disease. The arthritis, but not the skin condition, demonstrated dramatic response to anti-tumor necrosis factor immunotherapy.  (+info)

Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults. (2/19)

PRO 542 (CD4-IgG2) is a recombinant antibody-like fusion protein wherein the Fv portions of both the heavy and light chains of human IgG2 have been replaced with the D1D2 domains of human CD4. Unlike monovalent and divalent CD4-based proteins, tetravalent PRO 542 potently neutralizes diverse primary human immunodeficiency virus (HIV) type 1 isolates. In this phase 1 study, the first evaluation of this compound in humans, HIV-infected adults were treated with a single intravenous infusion of PRO 542 at doses of 0.2-10 mg/kg. PRO 542 was well tolerated, and no dose-limiting toxicities were identified. Area under the concentration-time curve, and peak serum concentrations increased linearly with dose, and a terminal serum half-life of 3-4 days was observed. No patient developed antibodies to PRO 542. Preliminary evidence of antiviral activity was observed as reductions in both plasma HIV RNA and plasma viremia. Sustained antiviral effects may be achieved with repeat dosing with PRO 542.  (+info)

Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team. (3/19)

The use of recombinant CD4-IgG2 in pediatric human immunodeficiency virus type 1 (HIV-1) infection was evaluated by single and multidose intravenous infusions in 18 children in a phase 1/2 study. The study drug was well tolerated, and dose proportionality was observed in terms of area under time-concentration curve and peak serum concentration. Acute decreases of >0.7 log(10) copies/mL in serum HIV-1 RNA concentration were seen in 4 of the 6 children treated with 4 weekly 10 mg/kg doses. At 14 days after treatment, 3 children had sustained reductions in serum HIV-1 RNA; the other children had rebounded to baseline levels or above. By 28 days after therapy, the peak HIV-1 cellular infectious units was reduced in all 6 children, including the 2 who had experienced an earlier transient increase in values. Thus, recombinant CD4-IgG2 treatment of HIV-1-infected children appears to be well tolerated and capable of reducing HIV-1 burden.  (+info)

Human immunodeficiency virus type 1 entry inhibitors PRO 542 and T-20 are potently synergistic in blocking virus-cell and cell-cell fusion. (4/19)

Human immunodeficiency virus type 1 (HIV-1) entry proceeds via a cascade of events that afford promising targets for therapy. PRO 542 neutralizes HIV-1 by blocking its attachment to CD4 cells, and T-20 blocks gp41-mediated fusion. Both drugs have shown promise in phase 1/2 clinical trials. Here, the drugs were tested individually and in combination in preclinical models of HIV-1 infection, and inhibition data were analyzed for cooperativity by using the combination index method. Synergistic inhibition of virus-cell and cell-cell fusion was observed for phenotypically diverse viruses for a broad range of drug concentrations, often resulting in > or = 10-fold dose reductions in vitro. Additional mechanism-of-action studies probed the molecular basis of the synergies. The markedly enhanced activity observed for the PRO 542:T-20 combination indicates that the multistep nature of HIV-1 entry leaves the virus particularly vulnerable to combinations of entry inhibitors. These findings provide a strong rationale for evaluating combinations of these promising agents for therapy in vivo.  (+info)

Structural flexibility and functional valence of CD4-IgG2 (PRO 542): potential for cross-linking human immunodeficiency virus type 1 envelope spikes. (5/19)

CD4-immunoglobulin G2 (CD4-IgG2) incorporates four copies of the D1D2 domains of CD4 into an antibody-like molecule that potently neutralizes primary human immunodeficiency virus type 1. Here electron microscopy was used to explore the structure and functional valence of CD4-IgG2 in complex with gp120. CD4-gamma2, a divalent CD4-immunoglobulin fusion protein, was evaluated in parallel. Whereas CD4-gamma2-gp120 complexes adopted a simple Y-shaped structure, CD4-IgG2-gp120 complexes consisted of four gp120s arrayed about a central CD4-IgG2 molecule, a structure more reminiscent of complement C1q. Molecular modeling corroborated the electron microscopy data and further indicated that CD4-IgG2 but not CD4-gamma2 has significant potential to cross-link gp120-gp41 trimers on the virion surface, suggesting a mechanism for the heightened antiviral activity of CD4-IgG2.  (+info)

Biochemical and biological characterization of a dodecameric CD4-Ig fusion protein: implications for therapeutic and vaccine strategies. (6/19)

Drug toxicities associated with HAART lend urgency to the development of new anti-HIV therapies. Inhibition of viral replication at the entry stage of the viral life cycle is an attractive strategy because it prevents de novo infection. Soluble CD4 (sCD4), the first drug in this class, failed to suppress viral replication in vivo. At least three factors contributed to this failure: sCD4 demonstrated poor neutralizing activity against most primary isolates of HIV in vitro; it demonstrated an intrinsic capacity to enhance viral replication at low concentrations; and it exhibited a relatively short half-life in vivo. Many anti-gp120 monoclonal antibodies, including neutralizing monoclonal antibodies also enhance viral replication at suboptimal concentrations. Advances in our understanding of the events leading up to viral entry suggest strategies by which this activity can be diminished. We hypothesized that by constructing a sCD4-based molecule that is large, binds multiple gp120s simultaneously, and is highly avid toward gp120, we could remove its capacity to enhance viral entry. Here we describe the construction of a polymeric CD4-IgG1 fusion protein. The hydrodynamic radius of this molecule is approximately 12 nm. It can bind at least 10 gp120 subunits with binding kinetics that suggest a highly avid interaction toward virion-associated envelope. This protein does not enhance viral replication at suboptimal concentrations. These observations may aid in the design of new therapeutics and vaccines.  (+info)

Human immunodeficiency virus type 1 attachment, coreceptor, and fusion inhibitors are active against both direct and trans infection of primary cells. (7/19)

Inhibitors of human immunodeficiency virus type 1 attachment (CD4-immunoglobulin G subclass 2), CCR5 usage (PRO 140), and fusion (T-20) were tested on diverse primary cell types that represent the major targets both for infection in vivo and for the inhibition of trans infection of target cells by virus bound to dendritic cells. Although minor cell-type-dependent differences in potency were observed, each inhibitor was active on each cell type and trans infection was similarly vulnerable to inhibition at each stage of the fusion cascade.  (+info)

In vivo efficacy of anti-glycoprotein 41, but not anti-glycoprotein 120, immunotoxins in a mouse model of HIV infection. (8/19)

Immunotoxins (ITs) targeting the HIV envelope protein are among the most efficacious antiviral therapies when tested in vitro. Yet a first-generation IT targeted to gp120, CD4-PE40 (chimeric immunotoxin using CD4 and the translocation and enzymatic domains of Pseudomonas exotoxin A), showed limited promise in initial clinical testing, highlighting the need for improved ITs. We have used a new mouse model of HIV infection to test the comparative efficacy of anti-HIV ITs targeted to gp120 or to gp41. Irradiated SCID/nonobese diabetic mice are injected with a tumor of human CD4(+) cells susceptible to infection and at a separate site persistently HIV-infected cells. The spread of infection from infected to susceptible tumor is monitored by plasma p24 and the presence of HIV-infected cells in the spleen. Anti-gp41 ITs in combination with tetrameric CD4-human Ig fusion protein have pronounced anti-HIV effects. Little if any anti-HIV efficacy was found with either CD4-PE40 or an Ab-targeted anti-gp120 IT. These data support continued exploration of the utility of ITs for HIV infection, particularly the use of anti-gp41 ITs in combination with soluble CD4 derivatives.  (+info)

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Other approaches in addition to existing treatment of HIV infection need to be evaluated. One approach may be to block HIV infection by interrupting the assembly of the virus within the cell or the budding of virus from the membrane of the infected cell. In addition, blocking the attachment of HIV to its cellular receptor may offer another point of attack. HIV binds to the CD4 receptor on the target T4 lymphocyte and the envelope glycoprotein of the virus (gp120) is capable of high affinity binding to CD4. Any agent that prevents the attachment of gp120 to the CD4 receptor should be able to block virus transmission and spread. Recently, scientists have succeeded in producing highly purified recombinant soluble human CD4. Recombinant CD4 is capable of binding to HIV envelope protein (gp120) and inhibiting HIV infectivity in test tube studies. Potential therapeutic benefit in patients with HIV infection could be derived from either or both of these biologic effects. In order to extend the length ...
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Other approaches in addition to existing treatment of HIV infection need to be evaluated. One approach may be to block HIV infection by interrupting the assembly of the virus within the cell or the budding of virus from the membrane of the infected cell. In addition, blocking the attachment of HIV to its cellular receptor may offer another point of attack. HIV binds to the CD4 receptor on the target T4 lymphocyte and the envelope glycoprotein of the virus (gp120) is capable of high affinity binding to CD4. Any agent that prevents the attachment of gp120 to the CD4 receptor should be able to block virus transmission and spread. Recently, scientists have succeeded in producing highly purified recombinant soluble human CD4. Recombinant CD4 is capable of binding to HIV envelope protein (gp120) and inhibiting HIV infectivity in test tube studies. Potential therapeutic benefit in patients with HIV infection could be derived from either or both of these biologic effects. In order to extend the length ...
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1. Brummel-Ziedins K, Orfeo T, Swords JN et al. Blood coagulation and fibrinolysis. In: Greer JP, Foerster J, Rodgers JM et al (eds). Wintrobes Clinical Hematology. Baltimore: Lippincott Wiliams & Wilkins 2009: 528-619. 2. Schmitt M, Harbeck M, Thomssen C et al. Clinical impact of the plasminogen activation system in tumor invasion and metastasis: Prognostic relevance and target therapy. Thromb Haemost 1997; 78: 285-296. 3. Silverman GA, Bird PI, Carrell RW et al. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins: evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem 2001; 276: 33293-33296. 4. De Bruin PA, Griffioen G, Verspaget HW et al. Plasminogen activators and tumor development in the human colon: activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas. Cancer Res 1987; 47: 4654-4657. 5. Duffy MJ. The urokinase plasminogen activator system: role in malignancy. Curr Pharm Des 2004; 10: ...
CD14 (also known lipopolysaccharide [LPS] receptor) is expressed strongly on monocytes and macrophages and weakly on the surface of neutrophils. CD14 (1-201 a.a.) is anchored to cells by linkage to glycosylphosphatidylinositol (GPI) and functions as a high affinity receptor for complexes of LPS and LPS binding protein (LBP). Soluble CD14, also binding to LPS, acts at physiological concentrations as an LPS agonist and has, at higher concentrations, an LPS antagonizing effect in cell activation. The myeloid differentiation antigen CD14 acts as the major receptor for bacterial LPS. The dominant form of the recombinant wildtype CD14 is the 50 kDa protein.,The rHuCD14 is produced from human CD14-transfected CHO-cells. Before transfection, the complete human CD14-cDNA was amplified by PCR and cloned into expression vector p-POL-DHFR ...
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... cd4 immunoadhesins MeSH D12.776.377.715.548.680.660.500 - immunoglobulin constant regions MeSH D12.776.377.715.548.680.745 - ... cd4 immunoadhesins MeSH D12.776.377.715.548.680 - immunoglobulin fragments MeSH D12.776.377.715.548.680.650 - immunoglobulin ...
... cd4 immunoadhesins MeSH D12.776.124.486.485.680.660.500 -- immunoglobulin constant regions MeSH D12.776.124.486.485.680.745 -- ... cd4 immunoadhesins MeSH D12.776.124.790.651.680.650 -- immunoglobulin fab fragments MeSH D12.776.124.790.651.680.650.500 -- ... cd4 immunoadhesins MeSH D12.776.124.790.651.680.660.500 -- immunoglobulin constant regions MeSH D12.776.124.790.651.680.745 -- ... cd4 immunoadhesins MeSH D12.776.124.486.485.680 -- immunoglobulin fragments MeSH D12.776.124.486.485.680.650 -- immunoglobulin ...
... cd4 immunoadhesins MeSH D12.776.395.550.200.250 -- cell adhesion molecules, neuronal MeSH D12.776.395.550.200.250.150 -- cell ...
... cd4 immunoadhesins MeSH D23.050.301.350.250 --- cell adhesion molecules, neuronal MeSH D23.050.301.350.250.150 --- cell ... cd4 MeSH D23.050.301.264.035.105 --- antigens, cd5 MeSH D23.050.301.264.035.107 --- antigens, cd7 MeSH D23.050.301.264.035.108 ... cd4 MeSH D23.050.301.264.894.101 --- antigens, cd5 MeSH D23.050.301.264.894.107 --- antigens, cd7 MeSH D23.050.301.264.894.108 ... cd4 MeSH D23.101.100.110.105 --- antigens, cd5 MeSH D23.101.100.110.107 --- antigens, cd7 MeSH D23.101.100.110.108 --- antigens ...
... cd4 immunoadhesins MeSH D12.776.543.550.200.250 -- cell adhesion molecules, neuronal MeSH D12.776.543.550.200.250.150 -- cell ... cd4 MeSH D12.776.543.750.925.700.605 -- receptors, ccr5 MeSH D12.776.543.750.925.700.650 -- receptors, cxcr4 MeSH D12.776. ...
CD4 Immunoadhesins at the US National Library of Medicine Medical Subject Headings (MeSH) Fletcher CV; DeVille JG; Samson PM; ... CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region. It ... "CD4 immunoadhesins in anti-HIV therapy: new developments". International Journal of Cancer. Supplement = Journal International ... CD4 is a surface receptor for human immunodeficiency virus (HIV). The properties of the protein means that it has potential to ...
"CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion ... Cho H, Chung YH (Aug 2012). "Construction, and in vitro and in vivo analyses of tetravalent immunoadhesins". Journal of ... Zhu X, Yang P, Zhou H, Li B, Huang X, Meng Q, Wang L, Kijlstra A (Oct 2007). "CD4+CD25+Tregs express an increased LAG-3 and ... The gene for LAG-3 lies adjacent to the gene for CD4 on human chromosome 12 (12p13) and is approximately 20% identical to the ...
"CD4 Immunoadhesins" by people in this website by year, and whether "CD4 Immunoadhesins" was a major or minor topic of these ... "CD4 Immunoadhesins" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "CD4 Immunoadhesins" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "CD4 Immunoadhesins". ...
CD4 Immunoadhesins. Antimetabolites. Molecular Mechanisms of Pharmacological Action. Reverse Transcriptase Inhibitors. Nucleic ... CD4-IgG is administered by IV bolus on day 16. Samples are drawn beginning 15-30 minutes prior to the injection of CD4-IgG. The ... Patients receive one IV bolus of CD4-IgG on day 1 and samples are drawn beginning 15-30 minutes prior to the CD4-IgG injection ... To determine the safety profile of recombinant human CD4-immunoglobulin G (CD4-IgG) and zidovudine (AZT) combination therapy in ...
AMENDED: Includes, as of 891201, an ancillary study entitled A Study of Recombinant CD4-Immunoglobulin G (CD4-IgG) Levels in ... Recently, scientists have succeeded in producing highly purified recombinant soluble human CD4. Recombinant CD4 is capable of ... Recently, scientists have succeeded in producing highly purified recombinant soluble human CD4. Recombinant CD4 is capable of ... is capable of high affinity binding to CD4. Any agent that prevents the attachment of gp120 to the CD4 receptor should be able ...
Designing CD4 immunoadhesins for AIDS therapy.. Capon DJ, Chamow SM, Mordenti J, Marsters SA, Gregory T, Mitsuya H, Byrn RA, ... CD4 immunoadhesins in anti-HIV therapy: new developments.. Chamow SM, Duliege AM, Ammann A, Kahn JO, Allen JD, Eichberg JW, ... Resistance of primary isolates of human immunodeficiency virus type 1 to soluble CD4 is independent of CD4-rgp120 binding ... Prevention of HIV-1 IIIB infection in chimpanzees by CD4 immunoadhesin.. Ward RH, Capon DJ, Jett CM, Murthy KK, Mordenti J, ...
Cd4 Immunoadhesins. Chimeric molecules resulting from the fusion of recombinant soluble CD4 to the Fc portion of ...
Designing CD4 immunoadhesins for AIDS therapy. Nature. 1989;337: 525-531.. OpenUrlCrossRefPubMed ...
al., (1989), "Designing CD4 Immunoadhesins for AIDS Therapy," Nature, 337:525-531. ... A genetically engineered HSA-CD4 hybrid has been shown to block the entry of the human immunodeficiency virus into CD4+ cells ... However, as with all fusion proteins, HSA-CD4 has a novel junction which can be immunogenic and contains T-cell epitopes ... Analysis of the junction between HSA and CD4 using the methods of Examples 1, 2, 3, and 4 identifies peptides with MHC binding ...
CD4 Immunoadhesins. publications Timeline , Most Recent This graph shows the total number of publications written about " ...
CD4 Immunoadhesins at the US National Library of Medicine Medical Subject Headings (MeSH) Fletcher CV; DeVille JG; Samson PM; ... CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region. It ... "CD4 immunoadhesins in anti-HIV therapy: new developments". International Journal of Cancer. Supplement = Journal International ... CD4 is a surface receptor for human immunodeficiency virus (HIV). The properties of the protein means that it has potential to ...
Capon et al., (1989), "Designing CD4 Immunoadhesins for AIDS Therapy," Nature, 337:525-531. ... Batra et al., (1993), "Insertion of Constant Region Domains of Human IgG1 into CD4-PE40 Increases Its Plasma Half-Life," ... Chaudhary et al., (1988), "Selective Killing of HIV-infected Cells by Recombinant Human CD4-Pseudomonas Exotoxin Hybrid Protein ...
CD4 Immunoadhesins 7. Fc Receptors (Fc Receptor) 8. Inosine Triphosphate (ITP) 9. Immunoglobulin G (IgG) ...
Designing CD4 immunoadhesins for AIDS therapy. Nature 1989;337:525-531.PubMedGoogle Scholar ... High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates ...
Designing CD4 immunoadhesins for AIDS therapy. Nature (London) 337:525-531.. OpenUrlCrossRefPubMed ... 7). We used MAbs that bind to CD4 binding site elements, the V3 loop, epitopes that are CD4 induced (CD4i), and the gp41 ... especially by antibodies that recognize CD4-induced epitopes and certain CD4-site binding antibodies. Our current studies also ... 7A), Fab M18 (whose epitope has not yet been defined, but it is not CD4 induced) (Fig. 7A), 447D and 391-95D (both bind to the ...
Capon, D., et al, "Designing CD4 Immunoadhesins for AIDS Therapy," Nature (Feb. 9, 1989) 337:525-531. ... CD4-GAMMA1 AND CD4-IgG1 CHIMERAS. WO1994006476A1. Sep 14, 1993. Mar 31, 1994. Immunex Corporation. Method of treating tnf- ... Ashkenazi, A., et al, "Immunoadhesins: An Alternative to Human Monoclonal Antibodies," A Companion to Methods in Enzymology ( ...
Designing CD4 immunoadhesins for AIDS therapy. Nature (Lond.) 337:525‐531.. Chou, T.C. 1991. Synergism and Antagonism in ... ATH8 (HTLV‐1 transformed tetanus‐toxoid‐specific CD4+ T cell clone; Mitsuya et al., ) or similar target T cells susceptible to ... High concentrations of recombinant soluble CD4 are required to neutralize primary HIV‐1 isolates. Proc. Natl. Acad. Sci. U.S.A ... Differences in the interaction of HIV‐1 and HIV‐2 with soluble CD4. J. Acquired Immune Defic. Syndr. 3:649‐657. ...
CD4 immunoadhesins in anti-HIV therapy: new developments. International journal of cancer. Supplement = Journal international ... Liposome targeting to human immunodeficiency virus type 1-infected cells via recombinant soluble CD4 and CD4 immunoadhesin (CD4 ... Resistance of primary isolates of human immunodeficiency virus type 1 to soluble CD4 is independent of CD4-rgp120 binding ... Conjugation of soluble CD4 without loss of biological activity via a novel carbohydrate-directed cross-linking reagent ...
... of Simian Immunodeficiency Viruses from Chimpanzees and Gorillas by Host Receptor Antibodies and CD4 Immunoadhesins. ...
... pneumocystis carinii OR enterocytozoon OR needlestick injuries OR pneumocystis carinii infections OR cd4 immunoadhesins OR ... OR hiv receptors OR cd4 antigens OR cd4-positive t-lymphocytes [tw] OR cd4-cd8 ratio OR receptors, ccr5 OR receptors, cxcr4 OR ... sp1 OR trichosanthin OR trimethoprim-sulfamethoxazole combination OR trimetrexate OR cd4 lymphocyte count OR cd4-positive t- ...
Designing CD4 immunoadhesins for AIDS therapy. Nature 337: 525-531. ...
... cd4 immunoadhesins MeSH D12.776.377.715.548.680.660.500 - immunoglobulin constant regions MeSH D12.776.377.715.548.680.745 - ... cd4 immunoadhesins MeSH D12.776.377.715.548.680 - immunoglobulin fragments MeSH D12.776.377.715.548.680.650 - immunoglobulin ...
Capon, D., et al., "Designing CD4 immunoadhesins for AIDS therapy", Nature 337: 525-531, Feb. 9, 1989. ... An alloreactive CD4+ human T cell clone designated PL1 stimulated with an anti-CD3 antibody exhibited 4-1BB/Fc binding. The ... The 4-1BB-L of the present invention also has been found to stimulate growth of CD3−CD4−CD8− immature lymphocytes. Cells ... 150:4338, 1993). Since TCC express 4-1BB, we assessed the effect of 4-1BB-L on the growth of the alloreactive CD4+ human T-cell ...
CD4 Immunoadhesins. *Cell Adhesion Molecules, Neuronal. *Integrin alphaXbeta2. *Intercellular Adhesion Molecule-1 ...
CD4 Immunoadhesins. *Cell Adhesion Molecules, Neuronal. *Integrin alphaXbeta2. *Intercellular Adhesion Molecule-1 ...
CD4 Immunoadhesins. *Cell Adhesion Molecules, Neuronal. *Integrin alphaXbeta2. *Intercellular Adhesion Molecule-1 ...
Immunoadhesins, CD4. *Immunoadsorbent Technic. *Immunoadsorbent Technics. *Immunoadsorbent Technique. *Immunoadsorbent ...
  • Low CD4 + cell counts, high antigen load from an opportunistic infection and a short interval between the treatment of an opportunistic infection and the start of ART are risk factors involved in the development of IRIS [ 5 , 6 ]. (ersjournals.com)
  • Briefly, there are two types of T cells (white blood cells produced in the t hymus), which are marked by the expression of CD4 or CD8 . (sulab.org)
  • Because CD4 cells are directly affected by HIV, the number of CD4 + cells in 1 cubic millimeter of blood is used as a measure of HIV progression. (sulab.org)
  • While deletion of the V2 loop renders the virus more susceptible to neutralization by antibodies that recognize diverse epitopes, in particular certain ones located in the CD4 binding site and the V3 loop, deletion of the V1 loop renders the virus refractory to neutralization, especially by antibodies that recognize CD4-induced epitopes and certain CD4-site binding antibodies. (asm.org)
  • Introducción: La infección por citomegalovirus (CMV) es frecuente en adultos con virus de inmunodeficiencia humana (VIH). (bvsalud.org)
  • If you'll permit me to anthropomorphize a bit, the virus first grabs onto the CD4 region like it would to CD4-Ig, but then it grabs onto CCR5, rendering it completely incapable of binding to a real CD4/CCR5- expressing T cells! (sulab.org)