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)

In order to develop recombinant Mycobacterium bovis BCG into a useful multivaccine vehicle, we established a foreign antigen secretion system in mycobacteria in which an extracellular alpha antigen of Mycobacterium kansasii was utilized as a carrier. By using this system, a B-cell epitope (Glu-12-Leu-Asp-Arg-Trp-Glu-Lys-Ile-19) of human immunodeficiency virus type 1 p17gag, which was identified by a fusion protein-based method, has been successfully obtained from BCG along with the alpha antigen. This is the first report of expression and secretion of a foreign viral antigen from BCG. It is possible that the system can become a universal vaccination vehicle applicable to protection against various infectious diseases.
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PMID:Establishment of a foreign antigen secretion system in mycobacteria. 170 18

In the central nervous system of AIDS patients, human immunodeficiency virus (HIV) infects primarily microglia, a cell type of bone marrow origin. Moreover, microglial cells isolated from adult human brain support the replication of macrophage-adapted strains of HIV type 1 (HIV-1) (B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Science 249:549-553, 1990). To determine whether the CD4 receptor, which is expressed in brain, mediates the entry of HIV-1 in microglial cells, we analyzed CD4 transcript expression in cultured microglia using highly sensitive polymerase chain reaction detection of cDNAs synthesized from RNA. With this method, CD4 transcripts could be detected in cultured microglia--as well as in various human brain regions and cultured macrophages used as positive controls--along with transcripts for the LDL and Fc receptors which are characteristic of cells of the macrophage lineage. We then attempted to block viral entry into microglial cells using anti-CD4 antibodies or soluble CD4 (sCD4), which recognize binding sites on CD4 and HIV-1 glycoprotein gp120, respectively. Cultures were pretreated with blocking antibodies (Leu-3a, OKT4A) or virus was preincubated with sCD4 prior to infection with HIV-1 strain AD87(M) or BaL. With either viral strain, these treatments resulted in the prevention of infection or significant and dose-dependent reduction in the number of infected cells and in the levels of reverse transcriptase or p24 antigen released in the medium. Thus, brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro.
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PMID:Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent. 170 42

Using a monoclonal antibody specific to the Lewis X antigen (anti-Lex), the authors studied 103 cases of Hodgkin's disease (HD) in comparison with 57 cases of non-Hodgkin's lymphoma (NHL); three cases of granulocytic sarcoma (GS); two cases of malignant histiocytosis (MH); one case of monoblastic leukemia (ML); one case of interdigitating reticulum cell sarcoma (IRCS); six cases of histiocytosis X (HX); one case of reticulohistiocytoma (RH); 44 various reactive conditions of the lymph node (LN). Reed-Sternberg and related (R-S) cells stained selectively in 80 of 92 cases of HD (87.0%), excluding 11 cases of lymphocyte predominance type. The stain was better in B-5-fixed specimens than in formalin-fixed specimens, showing a dense deposit of reaction products at a paranuclear site and on the cell surface. The staining results were compared with those of Leu-M1 and found to be superior both qualitatively and quantitatively (detection rate of R-S cells: 87.0% versus 68.5% of Leu-M1). Granulocytes, rare epithelioid histiocytes, and some endothelial and/or erythrocytes also stained with anti-Lex. The stain had positive results in three cases of GS showing a diffuse cytoplasmic staining pattern. Of NHL, two of 29 peripheral T-cell lymphomas stained to show rare paranuclear deposits without cell surface staining. The stain had negative results in MH, ML, IRCS, HX, and RH. Of 45 reactive LN, minute subcapsular collections of Lewis X+, altered-appearing Langerhans'-like cells, were observed in all ten LN from human immunodeficiency virus (HIV)-associated persistent generalized lymphadenopathy (PGL). The stain had negative results in all other various reactive conditions of LN. In conclusion, Lewis X staining is useful as a marker for R-S cells in paraffin sections with staining results superior to those of Leu-M1. Lewis X staining also detects subcapsular clustering of altered-appearing Langerhans'-like cells in PGL, which has not been described previously and warrants additional study.
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PMID:The Lewis X antigen. A new paraffin section marker for Reed-Sternberg cells. 170 18

Astrocytes are regarded as matrix of the neuron in central nervous system (CNS) and involve nutritional and supporting function of neuron. It was clarified that human and murine cultured astrocytes had Fc receptor (FcR) on their cell surface from the study of EA rosette assay, reverse ADCC (antibody dependent cellular cytotoxicity) and flow cytometric analysis with anti-FcR monoclonal antibodies (mAb) in this study. Human glioma cells express FcR III recognized by mAb MG 12 and mouse astrocytes express FcR II recognized by mAb 2.4 G 2. Expression of FcR on human astrocytes is compatible with FcR-mediated human immunodeficiency virus (HIV)-1 infection in CNS. Expression of adhesion molecules engaged in T and natural killer cell cytotoxicity was also investigated for human glioma cells. CD 56 (NKH-1 or Leu 19), which is an isoform of N-CAM (neural cell adhesion molecule) mainly distributed on human NK cells and a subset of T cells, was also expressed in neuroglial cells. LFA-3, a ligand for CD 2, but not ICAM-1, a ligand for LFA-1, was, expressed on glioma cells. So, CD 56 was suggested to be a new adhesion molecule in NK cell mediated lysis of glioma cells by their homotypic adhesive character.
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PMID:[Analysis of receptor expression on astrocytic cells]. 170 27

A quantitative rapid assay to detect resistant clinical human immunodeficiency virus type 1 (HIV-1) strains remains an important medical goal. A system incorporating a quantitative RNA.RNA hybridization assay that measures the amount of intracellular HIV-1-specific RNA has been employed to detect the level of inhibition by nucleoside analogues in sensitive and resistant HIV-1 strains. The RNA.RNA hybridization assay readily distinguished previously published zidovudine (ZDV; 3'-azido-3'-deoxythymidine)-resistant isolates from ZDV-sensitive isolates of HIV-1. The 50% inhibitory concentration (IC50) of ZDV for HTLV-IIIB and sensitive clinical HIV-1 isolates is between 0.01 and 0.04 microM. HIV-1 strains from three patients on long-term ZDV therapy displayed a greater than 20-fold increase in the ZDV IC50 compared to sensitive strains. The drug sensitivity system was confirmed by showing that mutations in the HIV reverse transcriptase gene from a ZDV-resistant isolate resulted in four amino acid changes (Leu-125----Trp, Ile-142----Val, Thr-215----Tyr, and Pro-294----Thr) including one change (Thr-215----Tyr) that has been previously reported to be associated with resistance. One clinical HIV strain with high-level ZDV resistance displayed a 5-fold increase in 2',3'-dideoxyinosine IC50 compared to that of HTLV-IIIB. A drug sensitivity assay employing RNA.RNA hybridization may be useful for extensive screening of HIV isolates from patients enrolled in clinical trials and permit the correlation of in vitro resistance with clinical outcome.
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PMID:Detection of human immunodeficiency virus type 1 clinical isolates with reduced sensitivity to zidovudine and dideoxyinosine by RNA.RNA hybridization. 170 32

A detailed immunologic study of three cases of sinus histiocytosis with massive lymphadenopathy (SHML) was performed to better characterize this rare disorder. One patient had prominent cervical lymphadenopathy that regressed spontaneously, whereas the other two patients had persistent cervical lymphadenopathy and recurrent infections. The first patient was otherwise healthy and had normal immunologic studies. One of the latter patients had a relative increase in blood B cells, a decreased level of serum immunoglobulin A (IgA), decreased blood lymphocyte mitogenic responses to multiple mitogens (37-42% of controls), and cutaneous anergy. The other patient with persistent disease also had a relative increase in blood B cells, polyclonal hypergammaglobulinemia, and circulating immune complexes, as well as decreased blood T cells and markedly decreased blood lymphocyte responses to mitogens (12-37% of controls). Immunohistochemical stains of the lymph nodes of the three patients revealed a characteristic phenotype for the sinus histiocytes: S-100 protein, 3/3; CD14 (Leu M3) 3/3; CD11c (Leu M5), 1/1; CD71 (OKT9), 3/3; CD4 (Leu 3a), 2/3; CD1a (OKT6), 1/3; alpha-1-antitrypsin, 3/3; alpha-1-antichymotrypsin, 3/3; CD35 (C3b), 1/1; CD11b (Mo1), 0/3; CD15 (Leu M1), 0/3; HLA-DR, 0/3; and lysozyme, 0/3. This phenotype suggests that the cells of SHML have features of both the Langerhans/interdigitating cell and mononuclear phagocyte lineages. Emperipolesis by the histiocytes of B cells, T cells, and natural killer cells was demonstrated by a double-staining technique. Our findings indicate that patients with SHML may have a variably expressed immunodeficiency that predisposes them to recurrent infections.
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PMID:Sinus histiocytosis with massive lymphadenopathy: a spectrum of disease associated with immune dysfunction. 171 75

The gastrointestinal tract is considered to be a major route of infection for the human immunodeficiency virus (HIV). To understand the interaction of HIV with epithelial cells of the intestinal mucosa, we have studied the infection of a human colon cancer cell clone HT-29-D4. The enterocyte-like differentiation of this clone can be modulated in vitro according to the concentration of glucose. We show that: (i) undifferentiated HT-29-D4 cells can be infected by HIV types 1 and 2 (HIV-1 and HIV-2) strains with no subsequent effect on cell growth; (ii) undifferentiated HT-29-D4 cells express a CD4-related antigen bearing epitopes of the immunoglobulin-like variable (V) region domains V1 and V2 of CD4 but lacking the epitope known to be involved in HIV envelope recognition; (iii) differentiated HT-29-D4 cells can be infected by HIV after an interaction with either the apical brush border membrane (luminal side) or the basolateral side (serosal side); (iv) the CD4-like molecule is restricted to the basolateral domain of differentiated cells; and (v) the infection is not inhibited by anti-CD4 monoclonal antibodies (mAbs) OKT4, OKT4A, Leu-3a, Bl4, 13-B-8-2, S-T4 or S-T40. We conclude that epithelial intestinal cells may represent a major site of entry for HIV. Infection of these epithelial cells may occur via the basolateral membrane by HIV-bearing lymphocytes or macrophages of the lamina propria and via the apical membrane by HIV present in the bowel lumen. This infection may remain silent for up to 9 months, and the virus can be rescued by cocultivation with lymphoid cells. These data may give an explanation for the long latent seronegative state that may occur in a HIV-infected individual.
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PMID:Human immunodeficiency virus can infect the apical and basolateral surfaces of human colonic epithelial cells. 171 4

A HLA-A3.1-restricted CD8+ cytotoxic T-cell clone, E7.20, that lyses cells infected with human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 768-778 (RLRDLLLIVTR, NL43 env sequence) of the cytoplasmic domain of gp41 by successive use of a panel of recombinant vaccinia viruses that express truncated env genes and synthetic peptides. The epitope is conserved on 7 (NL43, BRU, HXB2, BRVA, SC, JH3, and JFL) of 13 human immunodeficiency virus type 1 isolates from North America. Synthetic peptides of this region of strains RF and CDC4 are also recognized by E7.20 despite a nonconservative Thr----Val or Thr----Ala change at amino acid 777; however, an MN peptide, which has four amino acid substitutions, was not reactive. The epitope recognized by E7.20 has a predicted hydrophobic alpha-helical structure, with three contiguous Leu residues followed by Ile and Val at amino acids 772-776. Cytotoxicity was restricted by HLA-A3.1 using allogeneic target cells that shared HLA class I antigens with the donor and an HLA-A and -B negative human plasma cell line transfected with the HLA-A3.1 gene. The transfected cells were infectable by human immunodeficiency virus type 1 strains IIIB and MN but only the former virus sensitized them to killing by E7.20. The ability of E7.20 to specifically lyse a human lymphocyte line infected with a human immunodeficiency virus type 1 strain carrying the conserved epitope is consistent with an important role for cytotoxic T cells in controlling infection.
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PMID:Specific lysis of human immunodeficiency virus type 1-infected cells by a HLA-A3.1-restricted CD8+ cytotoxic T-lymphocyte clone that recognizes a conserved peptide sequence within the gp41 subunit of the envelope protein. 171 55

Sulfated polysaccharides (i.e., dextran sulfate) and sulfated polymers (i.e., sulfated polyvinylalcohol and sulfated copolymers of acrylic acid with vinylalcohol) were found to be potent and selective inhibitors of the replication of respiratory syncytial virus (RSV) and influenza virus type A (influenza A virus) but not of other myxoviruses (parainfluenza 3, measles, and influenza B viruses). The compounds were also inhibitory to human immunodeficiency virus type 1 (HIV-1) and HIV-2 and simian immunodeficiency virus but not simian AIDS-related virus. The mode of antiviral action of the sulfated polysaccharides and polymers can be attributed to an inhibition of virus binding to the cells (HIV-1), inhibition of virus-cell fusion (influenza A virus), or inhibition of both virus-cell binding and fusion (RSV). The fact that the sulfated polysaccharides and polymers are inhibitory to some myxoviruses and retroviruses but not to others seems to depend on the composition of the amino acid sequences of the viral envelope glycoproteins that are involved in virus-cell binding and fusion. All myxoviruses and retroviruses that are sensitive to the sulfated polysaccharides and polymers share a tripeptide segment (Phe-Leu-Gly). This tripeptide segment may be involved either directly (as a target sequence) or indirectly in the inhibitory effects of the compounds on virus-cell binding and fusion.
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PMID:Differential inhibitory effects of sulfated polysaccharides and polymers on the replication of various myxoviruses and retroviruses, depending on the composition of the target amino acid sequences of the viral envelope glycoproteins. 172 92

A strategy for the purification and cleavage of chimeric recombinant proteins based on a genetically engineered metal-binding peptide and a human renin cleavage site is described. Vectors were constructed to direct the synthesis of chimeric human immunodeficiency virus (HIV) reverse transcriptase (RT) or beta-galactosidase in Escherichia coli. As shown below, two control chimerics without the metal-binding peptide were also included: 1. Pro-Ile-His-Asp-His-Asp-His-Pro-Phe-His-Leu-Val-Ile-His-Ser-HIV RT 2. Pro-Ile-His-Asp-His-Asp-His-Pro-Phe-His-Leu-Leu-Tyr-Tyr-Ser-HIV RT 3. Pro-Ile-Pro-Phe-His-Leu-Val-Ile-His-Ser-HIV RT 4. Pro-Ile-Pro-Phe-His-Leu-Leu-Tyr-Tyr-Ser-HIV RT 5. Pro-Ile-His-Asp-His-Asp-His-Pro-Phe-His-Leu-beta-galactosidase Both N-terminal sequencing and an enzyme-linked immunosorbent assay utilizing antibodies to the metal-binding peptide were used to characterize the purified chimeric proteins. The relative RT activity of the chimeric protein was indistinguishable from the HIV-1 RT without the fusion sequence, indicating that the metal-binding and renin-cleavage sequences have no effect on the polymerase function of HIV-1 RT. The cleavage by recombinant human renin occurred at the expected site. A future paper will describe results on the use of genetically engineered alternating histidines in the purification of these chimerics by immobilized metal affinity chromatography.
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PMID:Expression and characterization of chimeric rDNA proteins engineered for purification and enzymatic cleavage. 172 60


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