Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C57BL/10ScCr mice are low responders to the alpha 1-6 epitope of dextran B512, although other C57BL mice are high responders. Both thymus-independent and thymus-dependent forms of dextran failed to induce an immune response in C57BL/10ScCr mice, but dextran functioned as a good carrier for antihapten responses in this strain. Dextran is a potent polyclonal B cell activator for cells from C57BL/10ScCr mice, although such cells are not activated by LPS. The C57BL/10ScCr mice possess the Igh-V gene coding for antibodies against dextran and the antidextran antibodies induced in (A X C57BL/10ScCr)F1 hybrids share an idiotype with antidextran antibodies produced in C57BL/10 mice. Bone marrow cells from C57BL/10ScCr mice do not respond to dextran when transferred into lethally irradiated C57BL/10 mice and C57BL/10 cells transferred into C57BL/10ScCr mice give a strong antidextran response. Thus, B cells having both the Igh-V gene coding for antibodies against dextran and activation receptors for dextran cannot be activated into antibody synthesis against any form of this immunogen. This determinant specific immunodeficiency suggests the existence of as yet unknown regulatory influences on Igh-V gene expression or B cell activation.
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PMID:Mechanism of unresponsiveness to the alpha 1-6 epitope of dextran B512 in a C57BL substrain. 619 Sep 81

The third variable domain (V3 domain) of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 contains a substantial number of positively charged amino acid residues. We previously demonstrated that mutation of basic amino acid residues at position 303, 306, 309, 313, and 325 in the V3 domain of HIV-1 strain NL4-3 resulted in a dramatic elimination of both virus infectivity and syncytium-inducing ability. Mutations of arginine at position 302 to serine (R302S) or lysine at position 320 to glutamine (K320Q) had variable effects on infectivity for a panel of T cell lines tested. These mutations are located on opposite sides of the Gly-Pro-Gly-Arg-Ala sequence in the center of the V3 domain. The R302S and K320Q mutations allowed us to determine if these basic residues are important for virus neutralization by polyanionic compounds. Dextran sulfate and heparin inhibited the cytopathogenicities of both mutants for MT-4 cells, although their 50% antiviral effective doses were slightly higher than those required to achieve complete protection against wild-type HIV-1NL4-3 replication. This result emphasizes that the basic amino acids of Arg302 and Lys320 are not essential for the inhibitory effect of dextran sulfate and heparin on HIV-1 infection.
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PMID:Single basic amino acid substitutions at position 302 or 320 in the V3 domain of HIV type 1 are not sufficient to alter the antiviral activity of dextran sulfate and heparin. 757 13

Dextran sulfate is a potent inhibitor of human immunodeficiency virus (HIV) binding and replication in lymphocytic cell lines. In this study, we demonstrate that the effect of dextran sulfate and heparin depends on the host cell type and on the V3 loop, the principal neutralizing determinant of HIV gp120. In particular, when dextran sulfate was tested on primary human macrophages infected with macrophage-tropic viruses, enhancement of infection was observed in 6 of 11 independent macrophage preparations and with 5 of 13 primary HIV isolates. Our in vitro observations might explain why enhanced HIV replication was observed in HIV-infected patients treated with dextran sulfate.
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PMID:Influence of host cell type and V3 loop of the surface glycoprotein on susceptibility of human immunodeficiency virus type 1 to polyanion compounds. 769 83

We prepared a series of modified proteins and peptides by derivatizing the positively charged epsilon-amino groups of the lysine amino acids through reaction with anhydrides of succinic acid (Suc) and aconitic acid (Aco). Human serum albumin (HSA) was modified by introduction of a single carboxylic group (Suc-HSA) or two carboxylic groups (Aco-HSA) per amine function, yielding strongly negatively charged compounds. The in vitro anti-human immunodeficiency virus (HIV)-1 IC50 of Suc-HSA was about 1 microgram/ml, and the most polyanionic modified albumin of the series (Aco-HSA) exhibited an IC50 as low as 0.02 microgram/ml. Similar derivatization of the plasma protein orosomucoid or the synthetic polypeptide polylysine did not produce compounds with significant anti-HIV-1 activity, indicating an HSA-specific effect. The mechanism of action of Suc-HSA was reported to be the inhibition of a post-binding virus-cell fusion event, probably due to interference with the gp41-mediated fusion process. In the present study we demonstrate that the more potent Aco-HSA also interferes with this fusion process but, additionally, this compound inhibits (i) the binding of soluble CD4 to HIV-infected cells, (ii) the binding of HIV particles to MT-4 cells, and (iii) the binding of anti-gp120 monoclonal antibody to the gp120 molecule. This indicates that Aco-HSA, apart from post-binding fusion, also inhibits virus-cell binding by shielding viral gp120. The simultaneous inhibition of binding and fusion may lead to a synergistic effect, explaining the extreme potency of Aco-HSA. The polyanionic HSAs are significantly less active against HIV-2 and do not interfere with the replication of feline immunodeficiency virus or 12 other DNA or RNA viruses, indicating a HIV-1-specific effect. In contrast, another polyanionic compound, the sulfated polysaccharide dextran sulfate, inhibits the replication of various viruses in a more nonspecific way, as a general polyanion. Dextran sulfate also exhibits strong anticoagulant activity, whereas Suc-HSA and Aco-HSA do not show this unwanted side effect.
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PMID:Novel, negatively charged, human serum albumins display potent and selective in vitro anti-human immunodeficiency virus type 1 activity. 790 28

Using the protein A plaque assay, the capacity of various polyclonal B cell activators to induce differentiation in human B lymphocytes was investigated. Dextran sulphate and native dextran were both virtually devoid of mitogenic properties. Lipopolysaccharide, however, was found to be a potent mitogen in human cells that, although giving rise to low DNA synthetic response, induced high numbers of immunoglobulin-synthesizing cells. Mean plaque-forming cell (PFC) numbers in healthy blood donors assayed on the optimal day (days 5-7) were 23,493 IgM/10(6) cells, 11,288 IgG/10(6) cells, and 2643 IgA/10(6) cells. Values obtained in spleen cells, peaking at days 4-6, were slightly higher. Purified protein derivative (PPD) was equally or even more effective than lipopolysaccharide (LPS) in generating PFC of different subclasses in peripheral blood with mean of 29,241 IgM/10(6), 21,269 IgG/10(6), and 3681 IgA/10(6). PPD furthermore induced a marked DNA synthetic response in human lymphocytes. These data suggest that LPS and PPD may both be used as functional markers in human cells when analysing patients with a suspected immunodeficiency state. It is suggested that cultures should be assayed using the protein A plaque assay, thereby being able not only to investigate the individual immunoglobulin classes but also to avoid the possible hazards involved in measuring antigen-specific responses in patients whose prior immunization to the antigen tested can never be totally excluded.
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PMID:Mitogenic activation of human lymphocytes: a protein A plaque assay evaluation of polyclonal B-cell activators. 953 23

Apheresis has been effective as rescue therapy in patients with severe, therapy-resistant, systemic lupus erythematosus (SLE). Its benefit in patients with less severe but therapy-resistant SLE is not known. Dextran sulfate apheresis was applied as a rescue therapy for therapy-resistant vasculitic skin lesions in a 30 year old female patient with a 9 year history of SLE in combination with antiphospholipid syndrome and Raynaud's phenomenon. Partial remission was achieved after 9 immunoadsorption sessions, as documented by marked improvement of skin lesions and an increase of capillary density in the nailfold area. Further improvement was noted with maintenance therapy using mycophenolate mofetil. Dextran sulfate apheresis can be applied safely in patients with moderate therapy-resistant SLE disease activity when severe immunodeficiency and cytotoxic adverse effects should be avoided.
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PMID:Dextran sulfate (Selesorb) plasma apheresis improves vascular changes in systemic lupus erythematosus. 1246 Apr 14


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