Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026916 (MAC)
 5,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sonicates of several Mycobacterium avium complex (MAC) strains isolated from acquired immunodeficiency syndrome (AIDS) patients were characterized in order to study the prominent antigens of these strains. Sonicates of 6-week-old cultures were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. A major 12 kDa glycoprotein antigen was observed in all the sonicates along with other proteins ranging up to 100 kDa. Western blotting, using the 12 kDa M. leprae 'specific' murine monoclonal antibody (MAb) MLO6, indicated the presence of a determinant in the 12 kDa antigen (in all the MAC isolates studied) which was immunologically cross-reactive with the 12 kDa antigen of M. leprae. The transparent variant of MAC 101 also demonstrated MLO6 reactivity while the opaque variant did not. Polyclonal antiserum raised against MAC 101 sonicate reacted with all the MAC isolates in immunodiffusion. These observations point to the cross-reactivity between these strains and suggest that they possess a M. leprae 'specific' determinant on a cross-reacting component which could be involved in virulence.
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PMID:Comparative antigenic analysis of Mycobacterium avium complex (MAC) isolates from AIDS patients. 129 16

We have isolated a murine myeloid precursor cell line (FDC-P1/MAC) that simultaneously expresses receptors for multi-CSF, GM-CSF, and M-CSF (c-fms protooncogene). FDC-P1/MAC cells express high levels of c-fms mRNA and protein when grown in M-CSF, whereas growth in multi-CSF or GM-CSF caused a dramatic reduction of c-fms glycoprotein and mRNA. Nuclear run-off assays demonstrated that c-fms transcription was not growth factor dependent and the regulation occurred posttranscriptionally. Factor switching experiments have shown that both multi-CSF and GM-CSF act dominantly and in a factor concentration dependent manner to suppress c-fms expression. In vitro agar assays of bone marrow cells grown in the presence of GM-CSF and M-CSF, individually and in combination, support the concept that GM-CSF can act dominantly to prevent monocyte/macrophage development. These results suggest that GM-CSF and multi-CSF can suppress development along the monocyte/macrophage lineage and offer a simple stochastic mechanism governing myeloid lineage restriction.
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PMID:Expression of the M-CSF receptor is controlled posttranscriptionally by the dominant actions of GM-CSF or multi-CSF. 170 92

The Authors discuss the etiologic, pathogenetic and immunopathologic aspects of Heymann nephritis, in order to compare the numerous acquisitions concerning this nephropathy with the scanty knowledge of human membranous nephropathy, of which it represents the experimental counterpart. This rat disease can be obtained by inoculation of tubular brush border preparations (active form) or of the relevant antibodies (passive form); after an initial hypothesis of glomerular deposition of circulating immune complexes, studies on its pathogenetic mechanisms, instead demonstrated that in situ immunoaggregates, caused by an interaction between circulating antibodies and fixed glomerular antigens, are formed. Recent investigations have led to the identification of a major nephritogenic antigen (gp330), which is a tubular brush border glycoprotein expressed by coated pits located at the glomerular epithelial cell surface. Studies on antigen-antibody interactions at this level have demonstrated that there is a quick redistribution and accumulation of the so-formed immune complexes, and when polyclonal antibodies were utilized, growth of subepithelial electron dense deposits was observed. Although other tubulo-glomerular antigens, which can also be expressed by endothelial cells, play an uncertain role, they seem to favour transmembrane passing of anti-gp330 antibodies. Immune complex formation gives rise to the onset of proteinuria through complement system activation, without leukocyte involvement: in particular a MAC and C9 fraction lytic effect was demonstrated on cultured epithelial cells. In conclusion, studies on Heymann nephritis contribute to our understanding of the etiopathogenetic mechanisms regarding human membranous nephropathy, and emphasize a possible role played by tubular antigens and in situ formed immune complexes.
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PMID:[Etiopathogenesis of membranous nephropathy: is there a correlation between experimental and human pathology?]. 248 93

The effector cell in mouse spleen which mediates natural cytotoxicity against mouse hepatitis virus (MHV)-infected target cells was characterized. The target cells were MHV-infected BALB/c 3T3, and the assay time was 3 hr. The effector cell, designated virus killer (VK) cell for the purpose of discussion, had the following phenotype: lymphocyte morphology, plastic-nonadherent, nylon wool-adherent, nonphagocytic, cyclophosphamide-sensitive; by antibody plus complement (C) depletion studies, it was asialo GM1-, NK 1.2 alloantigen-negative, Thy-1.2-, Lyt-5-, and macrophage antigen-negative; by rosetting techniques, it was Fc receptor-positive and surface Fab+; by flow cytometry (FACS) analysis, it was Lyt-2-, MAC-1-, Ia+, IgG (gamma)+, IgM (mu)+, IgD (delta)+, and B cell lineage antibody B-220+. NK cells, measured for cytotoxicity on YAC-1 cells, were similarly tested and were found to differ from the VK cell in the following properties: nylon wool-nonadherent, asialo GM1+, NK alloantigen-positive, Lyt-5+, surface Fab-, MAC-1+, Ia-, IgG-, IgM-, IgD-, and B-220-. The VK effector cell had a phenotype highly distinguishable from NK cells, effectors most commonly associated with antiviral natural cytotoxicity. The VK cell had a phenotype identical to that of a B lymphocyte and was identified as such. Although the effector cells displayed cell surface antibody, the antibody did not appear to be involved in lysis, because lysis could not be blocked by F(ab)'2 directed against Fab, mu, or delta. Cytotoxicity was more likely associated with recognition of the B lymphocyte surface by the MHV glycoprotein E2, as shown in the accompanying companion paper. This is the first demonstration that natural cytotoxicity can be mediated by B lymphocytes.
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PMID:Natural cytotoxicity against mouse hepatitis virus-infected cells. II. A cytotoxic effector cell with a B lymphocyte phenotype. 300 99

Eicosanoids play a prominent role in trauma. Such mediators of inflammation negatively influence cell-mediated immunity (CMI). There is, however, no information available on the effect of eicosanoids on a critical event in CMI, i.e., antigen-presenting (AP) cell function of macrophages (M luminal diameter), a cellular process responsible for the activation of T and B lymphocytes. The aim of this study, therefore, was to examine the effect of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) on AP cell function of the peritoneal M luminal diameter. To study this, a T-helper-cell clone, D10.G4.1 was employed. This cell clone proliferates in the presence of Iak (Class II glycoprotein, MAC product) bearing M luminal diameter and specific antigen (conalbumin A) thus directly reflecting the AP capability of the M luminal diameter. Peritoneal M luminal diameter were harvested from B10.BR mice (H2k) and their AP was tested in vitro by incubating varying numbers of M luminal diameter with 2 X 10(4) D10.G4.1 cells/well and conalbumin (400 micrograms/ml) in the presence and absence of different concentrations of PGE2 or TXB2. Cultures were incubated for 72 hr, pulsed with [3H]-thymidine, and harvested. At concentrations of 10, 30, and 100 nM of PGE2, D10.G4.1 proliferations were 38, 35, and 20% of control, respectively (P less than 0.05 compared to control). TXB2 added at the above-mentioned concentrations did not suppress the proliferative response of D10. Thus, PGE2 but not TXB2 has a potent immunosuppressive effect on AP of peritoneal M luminal diameter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin E2 depresses antigen-presenting cell function of peritoneal macrophages. 316 83

We describe here the major protein components of a highly purified human neutrophil plasma membrane fraction analyzed by uni- and two-dimensional gel electrophoresis, as well as their glycoprotein nature as determined by PAS staining, [125I]-Con A binding and [3H]-sodium borohydride labelling. A polypeptide of about 150 kDa appeared as the main Con A binding protein. The topology of the polypeptides has also been determined by protein labelling from the outside of the cell surface by lactoperoxidase catalyzed iodination and from within the bilayer by using the hydrophobic reagent [125I]-iodonaphtylazide. The antigenic features of some cell surface polypeptides have also been determined by the use of monoclonal antibodies. In this context we have detected by immunoprecipitation in human neutrophils the antigen MAC 120, previously found in monocytes and putatively associated with antigen presenting function.
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PMID:Human neutrophil plasma membrane. Specific labelling, topological distribution of proteins and surface antigen detection. 332 21

Lymphocytes from lymph nodes obtained from breast cancer patients undergoing mastectomy were fused with the 0467.3, UC729HF2, or KR-12 human cell lines, totaling 42 fusions with lymphocytes from 23 patients. A total of 1696 human-human hybridomas were generated, 675 (39.8%) of which produced human IgG and/or IgM. Seventy-three human hybridomas produced antibodies binding to autologous malignant breast tissue and/or MCF-7 cells, as assayed by immunohistology or by cell-binding enzyme-linked immunosorbent assay. Twelve of these hybridomas, all reacting with malignant breast tissue, were subcloned to stabilize the production of human immunoglobulin. The reaction patterns of these 12 human monoclonal antibodies were investigated further by immunohistology on formalin-fixed, paraffin-embedded tissues. The reaction patterns of the various antibodies showed substantial variation and the antibodies reacted with a varying frequency with antigens expressed by different malignant breast tumors. One of these antibodies, MAC 40/43 (IgM), reacted with malignant breast and colon carcinomas and other epithelial derived neoplasms but did not react with normal breast tissue or with other normal and malignant tissues tested, except for a weak reaction with certain normal epithelial tissues. The antigen defined by MAC 40/43 was identified as a Mr approximately equal to 47,000 glycoprotein.
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PMID:Human-human hybridomas and human monoclonal antibodies obtained by fusion of lymph node lymphocytes from breast cancer patients. 336 3

Since its introduction in 1987, zidovudine monotherapy has been the treatment of choice for patients with HIV infection. Unfortunately it has been established that the beneficial effects of zidovudine are not sustained due to the development of resistant viral strains. This has led to the strategy of combination therapy, and in 1995 treatment with zidovudine plus didanosine, or zidovudine plus zalcitabine, was demonstrated to be more effective than zidovudine monotherapy in preventing disease progression and reducing mortality in patients with HIV disease. Recent work demonstrates an even greater antiviral effect from triple therapy with 2 nucleosides, zidovudine plus zalcitabine with the addition of saquinavir, a new protease inhibitor drug. The HIV protease enzyme is responsible for the post-translational processing of gag and gag-pol polyprotein precursors, and its inhibition by drugs such as saquinavir, ritonavir, indinavir and VX-478 results in the production of non-infectious virions. As resistance may also develop to the protease inhibitors they may be used in combination, and future strategies may well include quadruple therapy with 2 nucleoside analogues plus 2 protease inhibitors. Administration of protease inhibitors alone or in combination with other drugs does raise a number of important pharmacokinetic issues for patients with HIV disease. Some protease inhibitors (e.g. saquinavir) have kinetic profiles characterised by reduced absorption and a high first pass effect, resulting in poor bioavailability which may be improved by administrating with food. Physiological factors including achlorhydria, malabsorption and hepatic dysfunction may influence the bioavailability of protease inhibitors in HIV disease. Protease inhibitors are very highly bound to plasma proteins (> 98%), predominantly to alpha 1-acid glycoprotein. This may influence their antiviral activity in vitro and may also predispose to plasma protein displacement interactions. Such interactions are usually only of clinical relevance if the metabolism of the displaced drug is also inhibited. This is precisely the situation likely to pertain to the protease inhibitors, as ritonavir may displace other protease inhibitor drugs, such as saquinavir, from plasma proteins and inhibit their metabolism. Protease inhibitors are extensively metabolised by the cytochrome P450 (CYP) enzymes present in the liver and small intestine. In vitro studies suggest that the most influential CYP isoenzyme involved in the metabolism of the protease inhibitors is CYP3A, with the isoforms CYP2C9 and CYP2D6 also contributing. Ritonavir has an elimination half-life (t1/2 beta) of 3 hours, indinavir 2 hours and saquinavir between 7 and 12 hours. Renal elimination is not significant, with less than 5% of ritonavir and saquinavir excreted in the unchanged form. As patients with HIV disease are likely to be taking multiple prolonged drug regimens this may lead to drug interactions as a result of enzyme induction or inhibition. Recognised enzyme inducers of CYP3A, which are likely to be prescribed for patients with HIV disease, include rifampicin (rifampin) [treatment of pulmonary tuberculosis], rifabutin (treatment and prophylaxis of Mycobacterium avium complex), phenobarbital (phenobarbitone), phenytoin and carbamazepine (treatment of seizures secondary to cerebral toxoplasmosis or cerebral lymphoma). These drugs may reduce the plasma concentrations of the protease inhibitors and reduce their antiviral efficacy. If coadministered drugs are substrates for a common CYP enzyme, the elimination of one or both drugs may be impaired. Drugs which are metabolised by CYP3A and are likely to be used in the treatment of patients with HIV disease include the azole antifungals, macrolide antibiotics and dapsone; therefore, protease inhibitors may interact with these drugs. (ABSTRACT TRUNCATED)
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PMID:Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. 908 59

Soluble (s) CD14, a marker for monocyte/macrophage activation and a mediator of bacterial lipopolysaccharide (LPS) action, was elevated in serum from human immunodeficiency virus type 1 (HIV- 1)-infected individuals (n = 92) compared with seronegative controls. The highest levels were found in patients with advanced clinical and immunological disease. Patients with ongoing clinical events had significantly higher sCD14 levels than symptomatic HIV-1-infected individuals without clinical events, with especially elevated levels in patients infected with Mycobacterium avium complex (MAC). On longitudinal testing of patients (n = 26) with less than 100 x 10(6) CD4 lymphocytes/L at baseline, we found that increasing sCD14 serum concentrations per time unit were associated with death, whereas no differences in CD4 cell number decrease were found between survivors and nonsurvivors. In vitro studies showed that HIV-1 glycoprotein 120 and purified protein derivative (PPD) from M avium (MAC-PPD) stimulated normal monocytes to release sCD14. Furthermore, MAC-PPD induced tumor necrosis factor (TNF) release from monocytes through interactions with CD14 and, importantly, the addition of sCD14 enhanced this MAC-PPD stimulatory effect. Our findings suggest that the CD14 molecule may be involved in the immunopathogenesis of HIV-1 infection, and it is conceivable that serial determination of sCD14 may give useful predictive information concerning disease progression and survival in HIV-1-infected patients.
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PMID:Elevated levels of serum-soluble CD14 in human immunodeficiency virus type 1 (HIV-1) infection: correlation to disease progression and clinical events. 973 Oct 66

90K/MAC-2BP glycoprotein is a serum tumour marker, member of the scavenger receptor cysteine rich (SRCR) protein superfamily, involved in different immunological mechanisms. In the present study, we determined 90K serum levels by a sandwich enzyme immunoassay using the same monoclonal antibody in 11 chronic active hepatitis (CAH), 48 liver cirrhosis and 36 hepatocellular carcinoma (HCC). In comparison, the same samples were also tested for AFP. According to a cut-off point of 14 micrograms/mL for the 90K, established as 100% of specificity in 50 controls, we observed increasing positivities from CAH to cirrhosis and then to HCC (27%, 50% and 78%, respectively). In cirrhotic patients 90K levels were associated with the presence of anti-HCV antibodies, but not with the degree of liver compromise. Finally, 90K sensitivity was higher than AIFP in all groups of hepatic patients. However, further investigations are needed before proposing 90K as a clinical useful tumour marker in the progression from cirrhosis to HCC.
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PMID:Serum 90K/MAC-2BP glycoprotein levels in hepatocellular carcinoma and cirrhosis. 1062 37


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