Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Blastogenic responses of normal human peripheral blood lymphocytes cultured in media supplemented with serum from children with kwashiorkor were, on average, 47.7% of those observed when the same cells were cultured in the presence of normal AB serum. Incorporation of radioactive uridine was also diminished in the presence of normal AB serum. Incorporation of radioactive uridine was also diminished in the presence of kwashiorkor serum indicating that lectin-induced RNA synthesis was also affected. The kwashiorkor serum effect was not due to a cytotoxic action nor could it be attributed to the presence of saccharides or other inhibitors of the inducing lectins. Mixing experiments showed that kwashiorkor serum was not inhibitory, but that it lacked factors present in normal serum that are required for optimal lymphocyte blastogenesis. The deficiency of these factors could largely be rectified by supplementing kwashiorkor serum with an ultrafiltrate of normal serum containing components with molecular weights of less than 500 Daltons. We conclude that nutritional deprivation of severity sufficient to cause kwashiorkor leads to a deficiency of low molecular weight lymphocyte growth factors. This lack may contribute to the immunodeficiency associated with the disease.
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PMID:Deficiency in kwashiorkor serum of factors required for optimal lymphocyte transformation in vitro. 45 81

In the present study we investigated to what extent the peripheral carbohydrate structure of N-linked glycans influences the antigenic properties of human immunodeficiency virus type 1 glycoprotein 120 (gp120). Recombinant gp120 was purified from GMK cells infected with a recombinant vaccinia virus expressing gp120. Purified gp120 was then coated onto 96-well ELISA microplates and subjected to sequential removal of peripheral monosaccharide units. Modified or unmodified gp120 was then incubated with monoclonal antibodies recognizing specific epitopes of gp120 and with a reporter lectin to determine the extent of carbohydrate elimination. Antibody and lectin binding was quantified in an enzyme-linked system. We found that the carbohydrate structure NeuAc-Gal beta (1-4) of N-linked glycans, defined both by lectin reactivity and by specific glycosidases, is involved in modulating the binding of antibody to a number of epitopes of peptide nature. The binding of antibody to one class of epitopes, situated in a region between amino acids 200 and 230, was strongly increased by removal of NeuAc-Gal beta (1-4), whereas the binding to epitopes in the V3 region was decreased and the binding to epitopes in the far N-terminal region was not altered by the treatment. These results suggested that peripheral structures of N-glycans are involved in modulating the overall conformation of gp120.
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PMID:Carbohydrate determinant NeuAc-Gal beta (1-4) of N-linked glycans modulates the antigenic activity of human immunodeficiency virus type 1 glycoprotein gp120. 128 69

A series of four mannose(Man)-, three N-acetylglucosamine (GlcNAc)n-, ten N-acetylgalactosamine/galactose(GalNAc/Gal)-, one 5-acetylneuraminic acid (alpha-2,3-Gal/GalNAc)- and one 5-acetylneuroaminic acid(alpha-2,6-Gal/Gal-NAc)-specific plant agglutinins were evaluated for their antiviral activity in vitro. the mannose-specific lectins from the orchid species Cymbidium hybrid (CA), Epipactis helleborine (EHA) and Listera ovata (LOA) were highly inhibitory to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in MT-4, and showed a marked anti-human cytomegalovirus (CMV), respiratory syncytial virus (RSV) and influenza A virus activity in HEL, HeLa and MDCK cells, respectively. The 50% effective concentration (EC50) of CA and EHA for HIV ranged from 0.04 to 0.08 micrograms/ml, that is about 3 orders of magnitude below their toxicity threshold (50% inhibitory concentration for MT-4 cell growth: 54 to 60 micrograms/ml). Also, the (GlcNAc)n-specific lectin from Urtica dioica (UDA) was inhibitory to HIV-1-, HIV-2-, CMV-, RSV- and influenza A virus-induced cytopathicity at an EC50 ranging from 0.3 to 9 micrograms/ml. The GalNAc/Gal-, alpha-2,3-Gal/GalNAc- or alpha-2,6-Gal/GalNAc-specific lectins were not inhibitory to HIV or CMV at non-toxic concentrations. CA, EHA and UDA proved to be potent inhibitors of syncytium formation between persistently HIV-1- and HIV-2-infected HUT-78 cells and CD4+ Molt/4 (clone 8) cells (EC50: 0.2-2 micrograms/ml). Unlike dextran sulfate, the plant lectins CA, EHA and UDA did not interfere with HIV-1 adsorption to MT-4 cells and RSV- and influenza A virus adsorption to HeLa and MDCK cells, respectively. They presumably interact at the level of virion fusion with the target cell.
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PMID:The mannose-specific plant lectins from Cymbidium hybrid and Epipactis helleborine and the (N-acetylglucosamine)n-specific plant lectin from Urtica dioica are potent and selective inhibitors of human immunodeficiency virus and cytomegalovirus replication in vitro. 132 50

Mannan-binding protein (MBP) is a lectin which, upon binding to certain carbohydrates, activates the classical pathway of complement without the involvement of antibody or C1q. Deficiency of the MBP is associated with an opsonic defect and recurrent infections during early life. An amino acid substitution in the exon 1 at codon 54 in the MBP gene (GGC [glycine] to GAC [aspartic acid]) has been shown to be closely associated with low MBP concentration in Caucasoids. The gene frequency of the mutant allele in this population has been estimated at 0.13. In the study described here, we investigated the association between the mutant allele and MBP protein concentration in Eskimos from East-Greenland and black Africans from the Baringo District in Kenya. The frequency of the GAC allele was identical in Eskimos and Caucasoids (0.13). No overlap with regard to MBP concentration between the genotypes was found in the Eskimos. In contrast, the Africans revealed a low frequency of the GAC allele (0.009). However, the median MBP protein concentration was approximately 5 times lower among the Africans than the Eskimos. In 12.6% of the Africans and in 2.5% of the Eskimos, MBP was undetectable. Thus, MBP deficiency is the most frequent immunodeficiency so far described. The high prevalence of MBP deficiency among healthy individuals indicates that MBP deficiency also confers some selective advantages. We advance the hypothesis that MBP deficiency is maintained in populations because MBP deficiency decreases the infectivity of some intracellular micro-organisms which are dependent on opsonization.
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PMID:Diallelic polymorphism may explain variations of the blood concentration of mannan-binding protein in Eskimos, but not in black Africans. 147 92

The lectin-like protein analogous to bovine conglutinin was purified from human serum. The carbohydrate-binding ability of conglutinin-like protein was inhibited by D-mannose, N-acetylglucosamine and L-fucose as well as by mannan-containing oligosaccharides. By applying a lectin-based ELISA system it was demonstrated that conglutinin-like protein binds to human immunodeficiency virus-1 (HIV-1) glycoprotein 120 (gp120) via its carbohydrate binding site. In vitro experiments with T-lymphoblastoid CEM cells revealed that conglutinin-like protein abolishes infection by HIV-1; a 50% cytoprotective concentration of 23.9 micrograms/ml was measured. These findings demonstrate that human conglutinin-like protein binds to HIV-gp120 and inhibits, under the described in vitro conditions, CEM cell infection.
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PMID:Inhibition of human immunodeficiency virus-1 infection by human conglutinin-like protein: in vitro studies. 161 96

The clinicoimmunological characteristics of three persons who died from bacterial meningoencephalitis is given. Appreciable immunodeficiency was recorded in patients with the grave disease course. The cerebral microglia of the same dead persons were subjected to a lectin histochemical examination. At the height of the disease the microglia proliferate, concentrate around the vessels, with their vascular pedunculi being swollen; microgliocytes with long processes arise. As the disease progresses, the microglia undergo irreversible changes characterized by the deformation and destruction of microgliocytes. Peanut lectin did not mark the microglia, indirectly negating its phagocytic function. In view of the data obtained it is suggested that drugs which potentiate the compensatory and adaptive reactions of the microglia and reduce the swelling of their vascular pedunculi be more widely used in patients afflicted with bacterial meningoencephalitis.
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PMID:[Use of lectins in histochemical examination of microglia of the human brain in bacterial meningoencephalitis]. 164 25

One hundred thirteen HSV-specific CD4+ T cell clones were established from the PBL of a healthy person and their functional heterogeneity was investigated. All clones proliferated in response to stimulation with HSV in the presence of autologous APC. Among those, 48 clones showed cytotoxic activity to HSV-infected autologous EBV-transformed lymphoblastoid cell line, but not to HSV-infected autologous fibroblasts, HSV-infected allogeneic cells, or K562 cells (group 1). Five clones showed cytotoxicity against HSV-infected autologous cells as well as HSV-infected allogeneic cells and K562 cells (group 2). The cytotoxicity of these clones was found to be mediated by the direct killing but not by the "innocent bystander" killing of target cells. Sixty clones showed no cytotoxic activity, however, among these, 23 revealed HLA-unrestricted and nonspecific cytotoxicity in the presence of PHA in culture (group 3), and the remaining 37 did not show any cytotoxic activity even in the presence of PHA (group 4). The cytotoxic patterns of these clones did not change in activated and resting phases, suggesting that the difference in cytotoxic ability does not depend on cell cycles. The cytotoxic activity of group 1 was inhibited by addition of anti-HLA-DR or anti-CD3 mAb to the culture, whereas these mAb had no effect on the cytotoxicity of group 2. All four groups of clones had helper activity for anti-HSV antibody production by autologous B cells. Moreover it was found that all groups of clones simultaneously produced IL-2, IL-4, and IFN-gamma after culture with APC followed by HSV Ag stimulation. The surface phenotype of all clones was uniformly CD2+, CD3+, CD4+, CD8-, CD29+, CD45RA-, but expression of Leu 8 was varied. These data therefore indicate that HSV-specific human CD4+ T cells are classified into at least four groups according to the presence and specificity of cytotoxicity, i.e., Th cells with HSV-specific and HLA-class II-restricted cytotoxicity, Th cells with HLA-unrestricted and nonspecific cytotoxicity, Th cells with lectin-dependent cytotoxicity, and Th cells without cytotoxic activity. The present finding of functional heterogeneity among virus-specific human CD4+ T cells might shed light on the pathogenesis of CD4+ T cell immunodeficiency, such as human retrovirus infections.
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PMID:Functional heterogeneity among herpes simplex virus-specific human CD4+ T cells. 167 4

Growth hormone (somatotropin) is a potent anabolic protein currently being evaluated clinically in cachexia associated with malignancy and human immunodeficiency virus (HIV) disease. Growth hormone can also lead to enhancement of lectin-mediated cellular proliferation, macrophage activation, and cytokine induction, events linked to induction of latent HIV in vitro. We thus explored the ability of recombinant human growth hormone (rhGH) to affect viral replication in acute and chronic HIV infection, and to alter transcription at the HIV-1 long terminal repeat (LTR). A clone of promonocytic cells, chronically infected with HIV-1 and susceptible to viral induction by a variety of cytokines and protein kinase C activators, was unperturbed by rhGH used over broad concentrations (10 to 500 ng/mL) and time intervals. This unresponsiveness paralleled the lack of effect of rhGH on HIV-associated trans-activation in both monocytic and CD4+ T-cell lines. In contrast, rhGH enhanced viral replication in acutely infected peripheral blood mononuclear cells (PBMC) by twofold to 20-fold, albeit having no adverse effect on the antiviral efficacy of zidovudine (AZT). Augmentation of HIV growth correlated with stimulation of cellular DNA synthetic responses and an increase in tumor necrosis factor-alpha (TNF-alpha) secretion. These data are discussed in the context of ongoing clinical trials of rhGH in HIV-seropositive individuals with wasting syndromes.
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PMID:Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. 173 91

Cerebrospinal fluid samples from 14 human immunodeficiency type 1 (HIV-1) seropositive patients in various stages of HIV infection were tested for the presence of autoantibodies to an endogenous manose-binding protein, the cerebellar soluble lectin (CSL), which has recently been found to be detected in a high proportion of patients with multiple sclerosis. An immunoblotting test was used with rat CSL as antigen. Seven patients were positive for anti-CSL and seven were negative. The seven anti-CSL-positive patients had signs of intrathecal immunoglobulin G production measured as an elevated IgG index, while the seven anti-CSL-negative patients had a normal IgG index. There was no apparent relation between infectious stage and the presence of anti-CSL. Immunological reactions such as anti-CSL autoantibodies may be a similar pathogenic mechanism in HIV and multiple sclerosis brain disease.
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PMID:Cerebrospinal fluid anti-cerebellar soluble lectin antibodies in human immunodeficiency virus type 1 infection. 173 84

A recombinant vaccinia virus in which the transcription of the human immunodeficiency virus type 1 (BRU isolate) env gene is driven by the 11K late vaccinia promoter yields about 10-fold higher amounts of gp160 env protein upon infection of monkey cells than does a recombinant in which gp160 is expressed using the 7.5K early-late promoter. The gp160 was purified from detergent lysates of infected cells by lentil lectin affinity chromatography followed by immunoaffinity chromatography, and was obtained in yields of 1-2 mg/10(9) cells of material estimated to be about 70% pure. Pairs of rabbits were immunized with purified gp160 using either one of five different adjuvants or an immunostimulating complex. In all cases a substantial humoral immune response was obtained after boosting, including an activity that neutralized the homologous (BRU) isolate of HIV-1. In some cases, this activity also neutralized two distantly related isolates, SF2 and MN.
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PMID:Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus. 174 74


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