UMLS:C0021051 - FACTA Search

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the origin and pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL), we studied 14 cases in which Epstein-Barr virus (EBV) infection was not an etiologic factor. By histology, 8 of the specimens were of the small noncleaved cell type and 6 consisted of the large diffuse cell type. Southern analysis using a J(H) probe was consistent with a monoclonal B-cell tumor in 13 cases. To characterize the expressed Ig genes, we performed reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing of PCR products. Eight cases expressed IgM and 1 case expressed IgG. V(H)3 genes were found in 5 cases, V(H)4 genes in 3 cases, V(H)1 genes in 2 cases, and a V(H)7 gene in 1 case. The nucleotide homology to known germline V(H) genes ranged from 80% to 97%, suggesting significant somatic diversification of expressed V(H) genes. The large proportion of V(H)3-expressing lymphomas in this series corresponds to the frequency of V(H)3-expressing B cells in the peripheral blood from healthy and (recent) human immunodeficiency virus (HIV)-seropositve individuals and contrasts with the V(H)3 clonal deficit observed in late stages of HIV infection. Similar to the Ig heavy chain genes, the corresponding Ig light chain genes showed significant deviation from known germline gene sequences. The large proportion of V(H)3-expressing lymphomas as well as the high degree of somatic deviation from germline suggest that these EBV-negative lymphomas might arise from antigen-selected expanded B-cell clones before transformation. Further support for this hypothesis is provided by sequential Ig sequence analysis in 1 patient with large-cell lymphoma. It was shown that 3 years before the diagnosis of axillary lymphoma, there existed several B-cell clones in this patient's bone marrow. One of these clones present in the bone marrow expressed the same rearranged V(H) gene as the axillary lymphoma. Taken together, the current findings from Ig gene analyses suggest that activation of B cells in the early phase of HIV infection may be a predisposing factor for subsequent B-cell transformation.
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PMID:Evidence for early B-cell activation preceding the development of Epstein-Barr virus-negative acquired immunodeficiency syndrome-related lymphoma. 897 54

Fusion regulatory protein-1 (FRP-1) regulates virus-mediated cell fusion and induces poly-karyocyte formation of monocytes without any fusogen. We have recently reported that FRP-1 and the 4F2/CD98 heavy chain are identical molecules. Cell fusion in Newcastle disease virus (NDV)-infected HeLa cells was enhanced when cells were incubated with anti-FRP-1 MAb. Anti-FRP-1 MAbs also induced human immunodeficiency virus gp160-mediated cell fusion. However, HBJ127, an anti-FRP-1/4F2/CD98 MAb that enhanced cell fusion in NDV-infected cells, delayed human parainfluenza virus type 2 (HPIV-2)-induced cell fusion in HeLa cells, although these viruses belong to the same genus Rubulavirus. No anti-FRP-1 MAbs enhanced cell fusion in HPIV-2-infected HeLa cells. Anti-FRP-1 MAbs including HBJ127 showed no effect on virus growth and expression levels of virus-specific poly-peptides in HPIV-2-infected HeLa cells, indicating that the delay in cell fusion by an anti-FRP-1 MAb is not due to suppression of virus replication. When HeLa cells were transfected with an expression vector harbouring HPIV-2 HN and F genes, cell fusion was also suppressed by HBJI27, but the effect was weak in comparison with virus-infected cells. These data indicate anti-FRP-1 antibodies not only induce/enhance, but also inhibit/delay virus-induced cell fusion and therefore FRP-1 molecules are multifunctional.
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PMID:An anti-fusion regulatory protein-1 monoclonal antibody suppresses human parainfluenza virus type 2-induced cell fusion. 901 Feb 89

We report here a series of 16 highly malignant diffuse large B-cell lymphomas of the oral cavity with unique immunohistologic features. Fifteen of these developed in human immunodeficiency virus-positive patients. All cases displayed morphologic features of diffuse large-cell lymphomas but strikingly differed from them in that they showed a minimal or absent expression of the leukocyte common antigen as well as of the B-cell antigen CD20. Instead, the tumor cells showed a constant reaction with the plasma cell characteristic antibody VS38c and a frequent reaction with the CD79a antibody. This, in conjunction with a variable expression of cytoplasmic Ig and a monoclonal rearrangement of the Ig heavy chain gene in all of the three tested cases confirmed the B-cell nature, the clonal origin, and the plasmacellular differentiation of these neoplasms. The majority of these tumors were negative for the BCL-6 protein, with the remaining cases showing only a partial and weak expression of this antigen. An association with the Epstein-Barr virus (EBV) was found in 9 of 15 tested cases showing abundant EBV-encoded nuclear RNA transcripts in the absence of EBNA-2. Five of the EBV-positive cases variably expressed LMP-1. We propose to name these tumors plasmablastic lymphomas, in accordance with their morphologic and immunohistologic features. Knowledge of this lymphoma entity is important to avoid confusion with nonlymphoid malignancies due to the lack of commonly used lymphoid markers.
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PMID:Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. 902 65

Haematopoietic stem cell transplantation has been used for the treatment of many different malignant and non-malignant diseases. The immune system of transplant recipients must be regenerated from the transplant inoculum, and it is not surprising that many transplant recipients are deficient in generating specific antibody responses to exogenous stimuli. This B cell immunodeficiency in these patients is associated with clinically significant infections, although the underlying mechanism remains unknown. We have previously shown that the pattern of usage of V(H) genes was similar between healthy subjects and BMT recipients, indicating that the immunodeficiency was not due to a dramatic imbalance in V(H) utilization. However, motif-specific hybridization analysis indicated that the accumulation of somatic mutations was much greater among rearrangements in controls than in BMT recipients. The failure of BMT recipients to accumulate somatic mutations in rearranged V(H) genes correlates with an absence of IgD- B cells, and is consistent with a defect in antigen-driven B cell responses. In the current study, which extends those findings, we have determined the nucleotide sequences of 68 heavy chain rearrangements from one patient as well as 39 rearrangements from a healthy control. Analysis of these sequences made possible a more precise definition of variable region configuration and of the status of somatic mutation in this BMT recipient. The results validate the hybridization data and support the conclusion that, although somatic hypermutation and, by inference, antigen-driven responses are detected in BMT recipients, they are deficient compared with healthy subjects as late as 1 year after transplant.
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PMID:Analysis of rearranged immunoglobulin heavy chain variable region genes obtained from a bone marrow transplant (BMT) recipient. 903 Aug 78

Neoplastic disease, especially malignant lymphomas, are often observed in cats infected with feline immunodeficiency virus (FIV). In order to clarify the characteristics of lymphoma cells and to investigate the pathogenesis in FIV-infected cats, we examined the lymphoma tissues developed in five cats naturally infected with FIV by Southern blot analyses using feline immunoglobulin (Ig), T-cell receptors (TCR) and FIV probes. All of the five cases were serologically positive for anti-FIV antibody and negative for feline leukemia virus antigen. Of these five lymphoma samples, two displayed rearrangement of the Ig heavy chain gene and deletion of the Ig light (kappa) chain gene, indicating that the tumor cells were committed to B-cell development. One tumor sample was identified as a T-cell lymphoma because of the presence of a rearranged TCR beta-chain gene. The other two cases were considered to be non-T non-B cell lymphoma because they did not show any rearrangement of the Ig and TCR genes. Therefore, no consistent tumor type was found in lymphoma cases infected with FIV. Clonal integration of FIV provirus was not detected in any of the five lymphoma samples obtained from FIV-infected cats using Southern blot analysis, although FIV proviral genome was detected in the genomic DNA of all the lymphoma samples by using a polymerase chain reaction (PCR). These results indicated that FIV might not play a direct role in tumorigenesis of lymphoma in cats.
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PMID:Molecular characteristics of malignant lymphomas in cats naturally infected with feline immunodeficiency virus. 926 55

The HLA-Cw3 heavy chain has been expressed at high level as insoluble protein aggregates in E. coli. The protein aggregates dissolved in strong denaturant solution were efficiently reconstituted by removal of denaturant in the presence of an HLA-Cw3 binding peptide (FAM) and beta 2m. The reconstituted HLA-Cw3/FAM protein binds specifically to a p58 natural killer cell inhibitory receptor, a natural ligand. The HLA-A2 molecule has also been reconstituted in complex with either of a peptide from myelin associated glycoprotein (MAG) or a peptide from the GAG protein of human immunodeficiency virus. The HLA-A2/MAG protein crystallized under the identical conditions as HLA-A2 purified from human lymphoblastoid cells. The reconstitution method has yielded an abundant supply of HLA molecules complexed with single antigenic peptides, and may be of general utility in reconstituting any class I MHC molecules. However, the HLA molecules could not be reconstituted either without a peptide or with an irrelevant peptide. Using this property, the reconstitution method could be used to determine whether a peptide is restricted/bound to certain class I MHC molecule.
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PMID:Reconstitution of class I MHC molecules expressed in E. coli and complexed with single antigenic peptides. 928 25

Intracellular antibodies (intrabodies) represent a new class of neutralizing molecules with a potential use in gene therapy. Intrabodies are engineered single-chain antibodies in which the variable domain of the heavy chain is joined to the variable domain of the light chain through a peptide linker, preserving the affinity of the parent antibody. Intrabodies are expressed inside cells and directed to different subcellular compartments where they can exert their function more effectively. The effects of intrabodies have been investigated using structural, regulatory, and enzymatic proteins of the human immunodeficiency virus (HIV-1) as targets. These intrabodies have demonstrated their versatility by controlling early as well as late events of the viral life cycle. In this article, we review studies of the use of intrabodies as research tools and therapeutic agents against HIV-1.
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PMID:Intracellular antibodies (intrabodies) for gene therapy of infectious diseases. 934 51

The intracellular targeting of recombinant antibodies is an experimental strategy to interfere with the function of selected molecules that is being utilized in a variety of different systems for research and medical applications. Since recombinant antibodies are increasingly being derived from phage display libraries, we have exploited phage technology to isolate, from a large combinatorial library, human antibody fragments directed against human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). We describe in this paper the in vitro and in vivo properties of a neutralizing anti-RT antibody fragment. We demonstrate that the heavy chain domain (VH-CH1) of the phage-derived antibody is able to inhibit the retroviral enzyme, in that it neutralizes the RNA-dependent DNA polymerase activity of HIV-1 RT. The VH-CH1 antibody fragment also neutralizes the activity of RT of drug-resistant HIV-1 mutants as well as that of murine retrovirus RT. To confirm the broad reactivity of the synthetic antibody fragment, we have assessed the ability of the intracellularly expressed VH-CH1 protein to interfere with murine retroviral infection. To this end, we developed an in vivo selection procedure based on the antibody-mediated resistance to a cytotoxic retrovirus and used this selection procedure to rescue, from a heterogeneous population, cells expressing the VH-CH1 antibody fragment. We finally demonstrate that the intracellular expression of the recombinant heavy chain antibody fragment leads to an efficient inhibition of viral retrotranscription by murine-based retrovirus.
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PMID:Inhibition of murine leukaemia virus retrotranscription by the intracellular expression of a phage-derived anti-reverse transcriptase antibody fragment. 934 80

In order to investigate the effect of primary amphipathic peptides on mollicutes (wall-less bacteria), we have synthesised five molecules (P1, P2, P3, JM123, and JM133) comprising a 16 to 18-residue hydrophobic sequence and the nuclear localization sequence (NLS) PKKKRKV of simian virus 40 large-T antigen, C-terminated by a cysteamide group. The hydrophobic cluster was in P1 the signal sequence of the heavy chain of Caiman crocodilus immunoglobulin G and in JM123 the fusion peptide of human immunodeficiency virus 1 glycoprotein gp41 in which phenylalanine7 was replaced by a tryptophan residue. The homologues P2, P3, and JM133 were obtained by slight alterations of these sequences. Circular dichroism spectroscopy revealed that, in liposomes, P-series peptides were mainly under the form of beta-sheets whereas JM-series peptides displayed a high proportion of turns. These peptides proved to be bactericidal for some mollicutes, notably Acholeplasma laidlawii, but were much less potent than melittin. Furthermore, their antibiotic activity was independent of the average thickness of the plasma membrane hydrophobic core whilst that of melittin was inversely related to the thickness. Melittin and the synthetic peptides abolished spiroplasma cell motility and helicity, but only melittin and P-series peptides split the cells into globular forms displaying an average diameter of ca. 1 microm. In contrast to melittin, the synthetic peptides agglutinated spiroplasmas, suggesting that their polycationic NLS was exposed on the cell surface. P-series peptides decreased, though less efficiently than melittin, A. laidlawii and Spiroplasma melliferum membrane potential (delta psi) and transmembrane pH gradient (delta pH), at concentrations much lower than their minimal inhibitory concentrations whilst JM-series peptides had no effect on delta psi and delta pH in the same conditions. Actually, the bactericidal activity of these peptides towards mollicutes was proportional to their ability to collapse the electrochemical transmembrane potential.
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PMID:Effects on mollicutes (wall-less bacteria) of synthetic peptides comprising a signal peptide or a membrane fusion peptide, and a nuclear localization sequence (NLS) -- a comparison with melittin. 937 27

A tetrameric recombinant major histocompatibility complex (MHC) class I-peptide complex was used as a staining reagent in flow cytometric analyses to quantitate and define the phenotype of Gag-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of simian immunodeficiency virus macaque (SIVmac)-infected rhesus monkeys. The heavy chain of the rhesus monkey MHC class I molecule Mamu-A*01 and beta2-microglobulin were refolded in the presence of an SIVmac Gag synthetic peptide (p11C, C-M) representing the optimal nine-amino acid peptide of Mamu-A*01-restricted predominant CTL epitope to create a tetrameric Mamu-A*01/p11C, C-M complex. Tetrameric Mamu-A*01/p11C, C-M complex bound to T cells of SIVmac-infected, Mamu-A*01(+), but not uninfected, Mamu-A*01(+), or infected, Mamu-A*01(-) rhesus monkeys. Specific staining of peripheral blood mononuclear cells (PBMC) from SIVmac-infected, Mamu-A*01(+) rhesus monkeys was only found in the cluster of differentiation (CD)8alpha/beta+ T lymphocyte subset and the percentage of CD8alpha/beta+ T cells in the peripheral blood of four SIVmac-infected, Mamu-A*01+ rhesus monkeys staining with this complex ranged from 0.7 to 10.3%. Importantly, functional SIVmac Gag p11C-specific CTL activity was seen in sorted and expanded tetrameric Mamu-A*01/p11C, C-M complex-binding, but not nonbinding, CD8alpha/beta+ T cells. Furthermore, the percentage of CD8alpha/beta+ T cells binding this tetrameric Mamu-A*01/p11C, C-M complex correlated well with p11C-specific cytotoxic activity as measured in both bulk and limiting dilution effector frequency assays. Finally, phenotypic characterization of the cells binding this tetrameric complex indicated that this lymphocyte population is heterogeneous. These studies indicate the power of this approach for examining virus-specific CTLs in in vivo settings.
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PMID:Analysis of Gag-specific cytotoxic T lymphocytes in simian immunodeficiency virus-infected rhesus monkeys by cell staining with a tetrameric major histocompatibility complex class I-peptide complex. 956 30

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