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)

Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of tumour-associated antigens. However, the aetiological significance of antigens and putative oncogenic viruses thus far identified in association with Hodgkin's disease remains to be clarified.
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PMID:The immunopathology of Hodgkin's disease. 15 50

To gain insight into a possible role for antibody-dependent cell-mediated cytotoxicity in vivo, we examined the ability of leukocytes from 28 patients with primary immunodeficiency and from 20 normal controls to lyse three different types of antibody-coated targets in vitro. Mean cytotoxic indices +/-1 SD elicited by unfractionated mononuclear cells from normal controls were 28.74+/-13.26 for human HLA antibody-coated lymphocyte targets, 42.79+/-8.27 for rabbit IgG antibody-coated chicken erythrocyte targets, and 47.58+/-10.34 for human anti-CD (Ripley)-coated O+ erythrocyte targets. Significantly (P=<0.05) lower than normal mean cytotoxic indices against lymphocyte targets were seen with effector cells from 10 patients with X-linked agammaglobulinemia (3.7+/-4.33), in 10 with common variable agammaglobulinemia (16.05+/-7.74), in 3 with immunodeficiency with hyper IgM (18.41+/-4.88), and in 2 with severe combined immunodeficiency (3.94+/-0.3). Antibody-dependent cytotoxicity against chicken erythrocytes was significantly (P=<0.05) lower than normal only in the common variable agammaglobulinemic group (33.33+/-12.3) and against human erythrocytes only in the common variable (34.36+/-9.59) and hyper IgM (27.54+/-0.66) groups. Rosette and anti-F(ab')(2) depletion studies with normal leukocytes indicated that a nonadherent, nonphagocytic, non-Ig-bearing, non-C receptor-bearing, Fc receptor-bearing lymphocyte was the only effector capable of lysing HLA antiboyd-coated lymphocyte targets. Patients with infantile X-linked agammaglobulinemia and severe combined immunodeficiency appear to have a marked deficiency in this type of effector cell function.
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PMID:Antibody-dependent cellular cytotoxicity in primary immunodeficiency diseases and with normal leukocyte subpopulations. Importance of the type of target. 61 6

Human monocyte-derived macrophages that express the CD4 molecule and the Fc receptor for IgG (Fc gamma R) play a major role in the pathogenesis of human immunodeficiency virus (HIV) infection. To explore this possibility further, human monoclonal antibody to glycoprotein 41 (gp41) was produced, and a heterobifunctional antibody composed of F(ab') x F(ab')2 fragments of monoclonal anti-gp41 and anti-Fc gamma RI 22.2 were constructed. Both antibodies were analyzed for neutralizing effects, and the role of the CD4 molecule in HIV infection was studied with human monocyte-derived macrophages. The bispecific antibody exhibited strong neutralizing properties, in contrast to the monoclonal anti-gp41 antibody. Moreover, in the presence of monoclonal anti-Leu-3a antibody, viral production was completely inhibited. These findings demonstrate the necessity of the CD4 molecule in HIV infection of human macrophages and emphasize the usefulness of such heterobifunctional antibody directed to virus and monocyte-derived macrophage Fc receptors in prevention of HIV infection.
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PMID:Bispecific antibody targeting of human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 to human macrophages through the Fc IgG receptor I mediates neutralizing effects in HIV-1 infection. 153 93

Subneutralizing concentrations of sera from human immunodeficiency virus (HIV)-1-infected patients augment HIV infection mediated by Fc receptor uptake by human monocytes and the monocytic cell line U937. Antibody-dependent enhancement (ADE) and neutralization activity were studied in the sera of HIV-1 antibody-negative volunteers who had been immunized with three 40-micrograms doses of a recombinant gp160 (rgp160) candidate HIV vaccine. Volunteers were vaccinated with rgp160 or a hepatitis B vaccine as a control on days 0, 30, and 180. Sera were obtained before and after three doses of vaccine and were tested for ADE and neutralization activity. Serum samples collected before vaccination showed neither neutralization nor ADE activity. Thirteen sera from volunteers who received gp160 and four from placebo recipients failed to show ADE. Three sera showed low levels of neutralization of strain IIIB of HIV. Vaccination with this dose of rgp160 produced neutralizing antibodies in some subjects but did not induce detectable enhancing antibodies.
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PMID:Studies of antibody-dependent enhancement of human immunodeficiency virus (HIV) type 1 infection mediated by Fc receptors using sera from recipients of a recombinant gp160 experimental HIV-1 vaccine. 153 59

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

We investigated monocyte-derived macrophage function in 25 HIV-positive patients, 19 in the CDC class III and 6 class IV; 17 were intravenous drug abusers (IVDA) and 8 were homosexual men. Macrophages from HIV-positive patients behaved normally in assays of superoxide anion (O2-) production and candidacidal activity. After 3 days' treatment with 200 U/ml recombinant interferon-gamma (rIFN-gamma) or 250 U/ml recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF), both control and HIV-positive patients' phagocytes expressed the activated state, as indicated by the increased O2- production in response to phagocytable or soluble stimuli; however, these cytokines did not enhance candidacidal activity. Compared to appropriate HIV-negative controls (18 healthy heterosexuals, 4 homosexuals and 4 IVDA), macrophages from 19 of the 25 HIV-positive patients presented a significant defect in their Fc receptor (FcR)-dependent phagocytosis, independently from the CDC stage, AZT therapy, or life style. Treatment of macrophages with rIFN-gamma impaired their capacity to ingest IgG-coated erythrocytes, both in controls and HIV-positive subjects. Treatment of phagocytes with rGM-CSF significantly increased their FcR-dependent phagocytosis in controls, whereas in HIV-positive patients and in HIV-negative homosexuals and IVDA only an upward tendency was observed. Although the mechanism of the impaired FcR-dependent phagocytosis in HIV-positive patients remain to be clarified, our results suggest that this functional defect may be secondary to phagocyte priming by circulating IFN-gamma in vivo. This macrophage alteration may be implicated in the immunodeficiency of HIV-positive patients. However, considering the potential role of FcRs in HIV infection enhancement, the defective FcR function might even be a protective mechanism against FcR-mediated HIV dissemination. In the light of these findings, the immunotherapeutic potential of IFN-gamma and GM-CSF in HIV infection merits further investigation.
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PMID:Monocyte-derived macrophage function in HIV-infected subjects: in vitro modulation by rIFN-gamma and rGM-CSF. 173 Jan 55

CD4 molecule, a surface marker of helper T lymphocytes, interacts with gp120 of human immunodeficiency virus (HIV) with a high affinity and, hence, serves as a virus receptor. Soluble chimeric CD4-immunoglobulin (Ig) possesses anti-HIV activity due to its binding activity to gp120. Furthermore, this recombinant molecule has unique Ig-like properties representing Fc receptor-binding activity and a long half-life in vivo. In this report we have thoroughly evaluated the effect of this compound on HIV infection using different in vitro systems. Treatment with 4 micrograms/ml of recombinant CD4-Ig after infection completely blocked the HIV-specific cytopathic effect, antigen expression, and virus release in MT-4 cells, a human T cell line which is highly susceptible to HIV. Similarly, this molecule blocked the HTLV-III/B and YU-1 strains of HIV infection in peripheral blood mononuclear cells even at 1 microgram/ml. Pretreatment of the Fc receptor-positive cell line U937 with this reagent resulted not in enhancement but again in blocking of HIV infection. About 95% of HIV infection was inhibited in U937 cells when cells were treated with this compound at the time of exposure to HIV. Recombinant-CD4-Ig also completely inhibited HIV-induced syncytia formation between MOLT-4 and MOLT-4/HIV and resulting virus release at 8 and 2 micrograms/ml, respectively. Due to its stability and long half-life, this compound could be a promising therapeutic agent against HIV infection.
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PMID:Evaluation of anti-human immunodeficiency virus effect of recombinant CD4-immunoglobulin in vitro: a good candidate for AIDS treatment. 178 69

It has been suggested that cofactors in human immunodeficiency virus (HIV) disease, particularly other viral infections, may accelerate progression to the acquired immune deficiency syndrome (AIDS). We have shown that in a population of 108 HIV-infected hemophiliacs observed for up to 9 years after the first documented HIV seroconversion, coinfection with cytomegalovirus (CMV) adversely influenced the course of the disease; in particular, logistic regression analysis showed that the age-adjusted relative risk of developing AIDS in CMV-seropositive patients was 2.5 times that in CMV seronegatives (p = 0.02). A number of potential mechanisms for the interaction of HIV and CMV have been proposed. Several groups have reported interaction at a molecular level between HIV and other viruses, including CMV, through transactivation of the HIV genome. Mechanisms by which the two viruses might gain entry to the same cell have been identified in vitro; these include Fc receptor-mediated uptake of antibody-coated HIV by CMV-infected fibroblasts. There is also some evidence that coinfection with HIV and CMV can occur in vivo, within brain cells. Interaction between these two viruses might also occur indirectly through the production of cytokines, such as tumor necrosis factor. Identification of cofactors in HIV infection may help in understanding the pathogenesis of AIDS, and may provide an important opportunity for intervention in the progression of the disease, particularly when an infectious agent for which specific therapy is available is identified.
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PMID:Cytomegalovirus as a possible cofactor in HIV disease progression. 184 22

The efficacy, toxicity, and mechanism of effect of intravenous Anti-D (Winrho) were studied in 43 Rh+ patients with immune thrombocytopenia purpura (ITP) who had not undergone splenectomy and in three already splenectomized patients. The mean platelet increase for the 43 nonsplenectomized patients was 95,000/microL (median 43,000/microL). Children had greater acute platelet responses than did adults. Human immunodeficiency virus status and duration of thrombocytopenia did not affect response. Maintenance treatment was given to patients as needed: the average interval between infusions was 24 days. The three splenectomized patients had no platelet response whatsoever. Toxicity was minimal; infusions were completed in less than 5 minutes. The generally accepted mechanism of effect of Anti-D has been Fc receptor blockade by substitution of antibody-coated red blood cells for antibody-coated platelets. Evidence is presented suggesting that the effect of IV Anti-D is not limited to Fc receptor blockade, including: (1) no correlation of parameters of hemolysis with platelet increase; (2) a 48- to 72-hour delay before platelet increase; (3) a tendency of the change in monocyte Fc receptor I expression to correlate with platelet increase; and (4) increased in vitro production of antibodies to sheep red blood cells following IV Anti-D infusion.
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PMID:Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. 191 92

The earliest preparations of immunoglobulins (Ig) decreased the susceptibility of agammaglobulinemic patients to infections caused by pneumococci, Haemophilus influenzae, meningococci, streptococci, and Pseudomonas aeruginosa. Intramuscular administration of such preparations was painful and traumatic, especially for children. Ethanol-fractionated Ig could not be administered intravenously (IV) because the IgG molecules tended to aggregate and thus were more likely to produce anaphylactoid reactions. New Ig preparations, isolated at low pH (e.g., pH 4) in the presence of traces of pepsin to inhibit reaggregation, were well tolerated when administered IV. Thus a new era of treatment and prophylaxis of disease using IV Ig (IVIG) was launched. The IVIG preparations revolutionized the management of virtually all immunodeficiency syndromes characterized by failure of antibody responses. Amelioration of antibody deficiency secondary to certain chronic diseases or surgical trauma can be achieved with these preparations. Newer uses of IVIG include treatment of some autoimmune diseases; in some conditions, the beneficial influences may be attributable to antiidiotype antibodies present in the IVIG. Another likely explanation is that IVIG inhibits damage to cells and tissues by antibody-mediated cellular cytotoxicity or blocks phagocytosis that is facilitated by Fc receptor mechanisms. The value of IVIG in preventing infection in patients undergoing bone marrow or organ transplantation and in the treatment and prophylaxis of life-threatening infections in neonates and premature infants also is reviewed.
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PMID:Historic aspects of intravenous immunoglobulin therapy. 187 38


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