Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The FACS-analysis of diseases as different as cancer, autoimmune disorders and chronic (retro)viral infections, including HIV-infection, shows -at least temporarily- a common feature of lymphocyte hyperactivation, characterized by cellular activation markers (HLA-DR, CD26, CD38, CD69, CD2R and/or CD30), as well as by solubilized membrane structures, such as beta-2m, sICAM-I, sIL-2R/sCD25, sCD8, and by some oversecreted immunocyte products (e.g. neopterin, lysozyme and/or cathepsin D). We tested two potential approaches to down-regulate the pathologically elevated CD8+ and HLA-DR+ T cells: (a) In animal model, we tested the sensibility of these, disease inducing and maintaining T cell subsets to in vitro pretreated (cell death preprogrammed) semi-syngeneic and allogeneic donor T cells in tumor-bearing mice. (b) In the first clinical study, we used a novel combination of FDA-approved drugs which inhibits Ca(2+)-influx and concomitantly down-regulates cytosolic cAMP in patient's overstimulated immunocompetent cells. We could achieve a 94.6-100% long-term survival in tumor-bearing mice. In patients, large primary tumors and large metastases shrinked by 80-85% and small metastases disappeared completely. Since in HIV-infected persons, the increased number of HLA-DR+ CD38+T (T8) cells is associated with a fall in CD4-level and with development of AIDS, we are looking for the elimination of these HLA-DR+ targets by our novel technique in two AIDS-simulating (FIV/FeLV and SIV) animal models.
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PMID:Treatment of solid tumors should obligatorily be combined with the in vivo codepletion of tumor-protecting, CD8+/HLA-DR(+)-suppressor T cells by alloreactive donor T cells whose preprogrammed cell death allows a high GvL-effect before GvHD can be established. Results of animal experiments, including more than 6000 mice. 873 48

The nuclear matrix plays a critical role in DNA replication, gene transcription and RNA processing. Transcriptionally active genes are usually associated with the nuclear matrix through DNA sequences, matrix attachment regions or MARs, which tether looped DNA to the matrix. In stable transfection and in transgenic mice MAR elements placed at the flanks of genic constructs may enhance expression and insulate against position effect variability, suggesting that independent units of transcription are established insulated from the regulatory controls of their neighbors. Herpes simplex virus type 1 (HSV-1) establishes lifelong latency in the infected host. Latency repression of viral genes extends to foreign genes incorporated into the viral genome. We report here a test of the hypothesis that MAR elements, flanking a foreign gene in the HSV-1 genome, would act to insulate it from latency repression, achieving long-term expression. A recombinant virus was produced which has an expression construct inserted into the HSV-1 genome at the Us3 locus. The expression construct consists of the A MAR element on one flank, an HIV-LRT driving the lacZ gene and the B MAR element on the other flank. The A MAR element is a 3 kb pair fragment of the 5' portion of the chicken lysozyme gene and the B MAR element is a 2.6 kb pair fragment from the 5' end of the human beta-globin gene locus control region. The LTR is derived from a human immunodeficiency virus isolated from the brain of an AIDS patient. Virus was stereotactically injected in the hippocampus, olfactory bulb and striatum of rat brains. Intense blue reaction product indicating beta-galactosidase activity was found in cells in each injected area at 2 days after injection. At 14 days after injection beta-galactosidase activity was no longer detected at any of the injected sites. We conclude that the MAR element construct did not escape latency repression.
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PMID:Incorporation of nuclear matrix attachment regions into the herpes simplex virus type 1 genome does not induce long-term expression of a foreign gene during latency. 887 33

The mechanisms accounting for T cell depletion in AIDS patients are not yet fully understood, nor are the roles of host factors in HIV pathogenesis. We show here that an ongoing humoral immune response to HIV gp120 can sensitize non-infected cells towards apoptosis. Thus, i.v. injection of 1 microg recombinant(r) gp120 into gp120-immunized human CD4-transgenic mice (huCD4 Tg), which express huCD4 on both T and B cells, results in T and B cell depletion in peripheral blood and lymphoid tissues. On day 6 after a bolus injection of gp120, the numbers of peripheral T cells and B cells in gp120-immunized huCD4 Tg decreased sevenfold and two- to threefold, respectively. Annexin V staining revealed a higher percentage of early apoptotic cells on day 1 of gp120 i.v. injection from gp120-primed huCD4 Tg spleens compared to gp120-primed controls. Boosting the primed huCD4 Tg mice with soluble gp120 and hen egg-white lysozyme led to lower secondary titers to both antigens than found in controls. Furthermore, splenocytes from gp120-pretreated immunized huCD4 Tg had a lower level of stimulation in response to anti-CD3 treatment. These in vivo results are consistent with in vitro data demonstrating that cross-linking CD4 on splenocytes of huCD4 Tg by rgp120SF2 and anti-gp120 not only sensitizes T cells for apoptosis, but also induces apoptosis per se, and suggest that anti-gp120 responsiveness can contribute to T cell depletion in AIDS.
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PMID:An ongoing immune response to HIV envelope gp120 in human CD4-transgenic mice contributes to T cell decline upon intravenous administration of gp120. 971 Feb 3

Multinucleated giant cells (MNGCs) expressing the human immunodeficiency virus (HIV) are characteristically found in hyperplastic tonsils and adenoids, acquired immunodeficiency syndrome encephalitis, vacuolar myelopathy, and lymph nodes coinfected with opportunistic pathogens. We identified similar polykaryons in the hyperplastic gut-associated immune system of an HIV-infected patient. Colonic biopsy specimens from this patient with heme-positive stools were studied by light and transmission electron microscopy (TEM), immunohistochemistry, and in situ hybridization for HIV-specific RNA. No bleeding source was identified by endoscopic or light microscopic examination of the biopsied tissues. There was diffuse and nodular lymphoid hyperplasia with germinal centers. HIV RNA-positive and p24 gag-positive Langhans'-type MNGCs and mononuclear cells (MNCs) were present within the lamina propria The MNGCs and MNCs were identified as macrophages on the basis of TEM and expression of CD68, HAM56, and lysozyme markers. They also expressed S100 protein, a marker of dendritic/Langerhans' cells, but they lacked Birbeck granules by TEM. In situ hybridization demonstrated RNA expression by MNGCs, MNCs, and follicular dendritic cells. TEM revealed budding and mature HIV particles on the plasma membranes of MNGCs, MNCs, and follicular dendritic cells. We conclude, therefore, that hyperplastic gut-associated immune systems can contain HIV-positive MNGCs and MNCs of the type seen in tonsils and adenoids and opportunistic pathogen-infected lymph nodes. Associated with immune activation, macrophages can express markers of dendritic/Langerhans' cells, cell types derived from the same CD34-positive bone marrow progenitor.
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PMID:Human immunodeficiency virus-rich multinucleated giant cells in the colon: a case report with transmission electron microscopy, immunohistochemistry, and in situ hybridization. 995 Jan 66

Lysozyme is well known for the ability to hydrolyze the cell wall of bacteria. Based on the similarity of structure between lysozyme and histones as seen from the results of X-ray crystal structure determinations, we have postulated that binding to nucleic acids may be another biological function of lysozyme. We have therefore begun a systematic study of the interactions of lysozyme and related molecules with nucleic acids, and present here a preliminary report. Binding to DNA and RNA has been demonstrated from gel electrophoresis, enzyme activity, and coprecipitation studies. We suggest that this function of lysozyme will provide an explanation why Lee-Huang et al. (1999) [Proc. Natl. Acad. Sci. USA 96, 2678-2681] were able to call lysozyme a "killer protein" against the AIDS virus, and may provide a new avenue of research on AIDS therapy.
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PMID:Lysozyme association with nucleic acids. 1060 May 9

We have determined that polymeric IgA in saliva of HIV-1-uninfected individuals binds in varying degrees to components of culture supernatants containing HIV-1 recombinant proteins when ELISA is used for the determination. This finding did not extend to salivary IgG antibodies. Further, such problems were not encountered in Western blot. Binding did not appear to be mediated by salivary proteins known to bind to IgA, including secretory component, amylase, lactoferrin, lysozyme, galactosyl transferase, or secretory leukocyte protease inhibitor, and was not influenced by blocking reagents or by changes in secondary anti-IgA antibodies. Although these findings will not likely impact on the use of saliva as a diagnostic fluid for HIV-1 infection (the HIV-1 response in saliva is mostly of the IgG isotype), they indicate that assessments of this secretion as an indicator of IgA mucosal immune responses to HIV-1 vaccines should be undertaken with caution.
AIDS Res Hum Retroviruses 2000 Apr 10
PMID:False positivity of enzyme-linked immunosorbent assay for measurement of secretory IgA antibodies directed at HIV type 1 antigens. 1077 50

The expansive use of immunosuppressive medications in fields such as transplantational medicine and oncology, the higher frequency of invasive procedures in an ageing population and the HIV/AIDS pandemic have increased the frequency of systemic fungal infections. At the same time, increased resistance of pathogenic fungi to classical antifungal agents has led to sustained research efforts targeting alternative antifungal strategies. In this review, we focus on two promising approaches: cationic peptides and the targeting of fungal virulence factors. Cationic peptides are small, predominantly positively charged protein fragments that exert direct and indirect antifungal activities, one mechanism of action being the permeabilization of the fungal membrane. They include lysozyme, defensins and cathelicidins as well as novel synthetic peptides. Among fungal virulence factors, the targeting of candidal secreted aspartic proteinases seems to be a particularly promising approach.
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PMID:Alternative approaches to antifungal therapies. 2307


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