Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.
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PMID:Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro. 137 63

The cytokines IL-6, IL-1, and TNF play a key role in the pathogenesis of rheumatoid arthritis (RA) and initiate hepatic serum amyloid A (SAA) expression after injury. To provide a possible mechanistic explanation for the previous observation that plasma SAA concentrations decreased during treatment of RA patients with tenidap, but increased during treatment with naproxen, the present study compared the effects of tenidap and naproxen on the two stages of SAA expression: cytokine production by human PBMC and cytokine-stimulated SAA synthesis by human Hep3B hepatoma cells. Tenidap inhibited production of IL-6 greater than TNF greater than IL-1; the effect of naproxen on production of all three cytokines was lesser and least on IL-6. Indeed, an increase in IL-6 production was observed after exposure to naproxen. PBMC beta-2-microglobulin production and total protein synthesis were unaffected at concentrations and times at which effects on cytokine production were observed. Cell density was a significant factor in the extent to which cytokines were stimulated by LPS. Approximately physiologic cell densities, 0.5 to 1 x 10(6) cells/ml, were optimal for stimulation of IL-1-beta and IL-6 production by LPS; however, greater amounts of TNF were produced at lower cell densities. Because neither tenidap nor naproxen inhibited SAA synthesis by cytokine-stimulated Hep3B cells and because they differ most significantly in their effect on IL-6 production, the results support a role for IL-6 in the continued stimulation of SAA production during RA.
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PMID:Modification of proinflammatory cytokine production by the antirheumatic agents tenidap and naproxen. A possible correlate with clinical acute phase response. 172 67

Serum levels of phospholipase A2 (PLA2) activity have been shown to be elevated in cases of septic shock and rheumatoid arthritis. The cellular origin of serum PLA2, however, is not known. In this report, we demonstrate that human group II PLA2 expression and secretion are induced in hepatoma cells (HepG2) following treatment with interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-1 (IL-1). Of the three cytokines, IL-6 is the most potent. Significant synergy is observed between IL-6 and IL-1 and between IL-6 and TNF, but not between IL-1 and TNF. PLA2 induction does not occur in human YT cells, which are known to have receptors for both IL-1 and IL-6, indicating that the regulatory mechanism involved is cell type-specific. The results of RNA blot analysis indicate that the PLA2 gene is regulated in HepG2 cells at the pretranslational level. Induction of PLA2 synthesis in HepG2 cells in response to these cytokines resembles the induction of the acute phase plasma proteins which are synthesized in cultured hepatocytes and hepatoma cells following exposure to the same cytokines and in liver in response to inflammation and infection. In addition, a putative IL-6-responsive element, which is homologous to a similar element found in several acute phase genes, is present in the 5'-promoter-proximal region of the PLA2 gene. These results suggest that serum PLA2 is synthesized in and secreted from liver cells in response to inflammatory stimuli, mediated primarily by IL-6, and therefore should be classified as an acute phase protein.
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PMID:Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. 184 31

We studied the prevalence of anti-HCV in 585 sera from various individuals, using enzyme immunoassay (EIA, Abbott Lab.). Anti-HCV was detected in 16 (10.7%) out of the 150 patients with HBsAg positive liver diseases diagnosed by liver biopsy and they consisted of none out of 10 acute viral hepatitis, 3 out of 15 chronic persistent hepatitis, 4 out of 50 chronic active hepatitis, 2 out of 32 liver cirrhosis, and 7 out of 43 hepatocellular carcinoma. Anti-HCV was detected in 43 (45.3%) out of 95 patients with HBsAg negative liver diseases diagnosed by liver biopsy and they consisted of 5 out of 8 acute viral hepatitis, 2 out of 10 chronic persistent hepatitis, 17 out of 30 chronic active hepatitis, 4 out of 15 liver cirrhosis, and 15 out of 32 hepatocellular carcinoma. Anti-HCV was detected in 22 (38.6%) out of 57 hemodialysis patients, in 3 (6.7%) out of 45 kidney transplants, in 2 (11.1%) out of 18 fatty liver diagnosed by liver biopsy, in 2 (1.3%) out of 150 healthy blood donors, in none out of 40 healthy volunteers, in 6 (31.6%) out of 19 rheumatoid arthritis and in 6 (54.5%) out of 11 systemic lupus erythematosis cases. There were familial clusters of chronic liver diseases in 4.7% of patients with HBsAg negative/anti-HCV positive chronic liver diseases, while in 19.4% of patients with HBsAg positive/anti-HCV negative liver diseases. Incidence of anti-HCV within patients with HBsAg positive liver diseases was higher in HBsAg negative patients than in HBsAg positive patients (17.6% and 10.3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Seroprevalence of antibody against hepatitis C virus (anti-HCV) in various groups of individuals in Korea. 190 58

A micro-enzyme linked immunosorbent assay (micro-ELISA) has been evaluated as a diagnostic test to detect amoebic antigen in polyethylene glycol (PEG) precipitated circulating immune complexes (CIC) in sera from patients with amoebiasis. The immune complexes were captured on rabbit anti-amoebic IgG-coated wells of microtitration plates and the complexed antigen was detected by enzyme linked antihuman immunoglobulins. A titre of greater than 160 for the immune complexes was considered to be of clinical significance. The immunoassay detected amoebic, antigen-specific CIC in 35 (94.5%) of 37 patients with confirmed amoebic liver abscess. Twenty (55.5%) of 36 clinically suspected cases of amoebic liver abscess had amoebic antigen-specific CIC and responded favourably to anti-amoebic chemotherapy. Only two (20%) of 10 cases of non-dysenteric symptomatic intestinal amoebic infection had amoebic antigen-specific CIC. One (10%) of 10 patients with non-amoebic intestinal disorders also had amoebic antigen in CIC. However, none of 15 cases of non-amoebic hepatic disorders that included hydatid disease, metastatic adenocarcinoma, hepatocellular carcinoma, cholecystitis and choledocal cyst, 13 cases of rheumatoid arthritis and 25 apparently healthy subjects had amoebic antigen in CIC. The levels of the amoebic antigen-specific CIC did not correlate (p greater than 0.05) with either the number of abscess(es) or lobe(s) of the liver involved. However, the levels of antigen-specific CIC were higher (p less than 0.01) in patients with a liver size of more than 5 cm below the right costal margin. Antigen-specific CIC levels tended to decline or disappear during 3-6 months following completion of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uses and limitations in the demonstration of specific circulating immune complexes in patients with amoebiasis. 235 92

A radioimmunometric technique for the detection of autoantibodies to liver membrane antigens has been developed using Alexander cells, a human hepatocellular carcinoma cell line. After incubation of Alexander cells with serum, antimembrane antibodies were detected by addition of 125I-labeled Protein A. Binding ratios in 15 children with uncontrolled autoimmune chronic active hepatitis and in seven children with primary sclerosing cholangitis were significantly higher than in 18 age-matched normal controls. Nine patients with inactive autoimmune chronic active hepatitis, 13 with alpha 1-antitrypsin deficiency and five with fulminant hepatic failure had ratios similar to controls. In nine patients with Wilson's disease, there was a modest but significant increase in binding ratio. In four children with autoimmune chronic active hepatitis, binding ratios fell during effective immunosuppressive therapy. Sera from patients with systemic lupus erythematosus or rheumatoid arthritis gave normal results, excluding that binding derives from Fc-mediated immune complex capture. A positive correlation was found between Alexander cell binding values and anti-liver-specific protein antibody titers, suggesting that the two assays detect antibodies against shared antigenic determinants. The Alexander cell assay is a simple, rapid and sensitive technique to detect antibody to liver cell membrane antigens.
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PMID:Detection of anti-liver cell membrane antibody using a human hepatocellular carcinoma cell line. 253 48

This review on the risks and benefits of oral contraceptives clarifies the risks and misperceptions, and discusses 10 potential health benefits. In the U.S. where maternal mortality is about 20.6/100,000, the risk of death from pills ranges from 1.8 for nonsmokers to 6.5 for smokers. It is likely that most of the small existing mortality risk of pill use is due to thromboembolism. Atherosclerosis, the major cause of death for U.S. women, may be reduced by the pill. It is still controversial whether pills increase risk of hepatocellular carcinoma and malignant melanoma; they protect against endometrial cancer (the 3rd greatest cancer killer) and ovarian (the 4th) cancer; they may increase risk slightly in some subgroups for breast and cervical cancer, although data are conflicting. Pills also protect against ectopic pregnancy, benign breast disease, pelvic inflammatory disease, ovarian cysts, iron deficiency anemia and possibly uterine fibroids and osteoporosis. It is no longer held that orals protect against toxic shock syndrome or rheumatoid arthritis. It is estimated that oral contraceptives avert 50,000 hospital admissions per year in the U.S.
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PMID:The health effects of oral contraceptives: misperceptions, controversies, and continuing good news. 266 76

We have looked for IL-6, a cytokine that has immunomodulating and inflammation-associated activities, in joint exudates (fluid and mononuclear cells) from patients with rheumatoid arthritis and other arthritides using both biologic and biochemical assays. IL-6 was assessed by its ability to stimulate alpha 1-antichymotrypsin secretion from the human hepatoma cell line Hep3B clone 2, an activity which is blocked by an antiserum to Escherichia coli derived IL-6, and by the growth of the IL-6-dependent murine hybridoma 7TD1 cell line. IL-6 isoforms in synovial fluid were characterized by immunoaffinity chromatography followed by Western blotting. The presence of IL-1 in synovial fluids and its production by synovial fluid mononuclear cells was monitored by Western blotting and indirect immunofluorescence with polyclonal anti-IL-1 beta antisera. In an analysis of 30 effusions from 27 rheumatoid patients with acutely inflamed joints, abundant quantities of IL-6 (greater than 2 ng/ml) were detected in 23 by the alpha 1-antichymotrypsin bioassay. Several rheumatoid synovial fluids also had elevated IL-6 levels in the 7TD1 bioassay. Seven of nine nonrheumatoid effusions also contained high levels of IL-6 (greater than 2 ng/ml). No IL-1 (less than 0.25 ng/ml) could be detected by Western blotting in 10 rheumatoid effusions even though eight of these contained high levels of IL-6. The IL-6 activity could be neutralized with a rabbit antiserum to rIL-6. Multiple IL-6 isoforms (25, 30, 45 kDa) were present in two rheumatoid and one traumatic effusion studied. Fresh mononuclear cells isolated from various synovial effusions did not appear to make IL-6 constitutively, as no IL-6 could be detected in the media of cells cultured for 12 to 18 h after isolation. Similarly, there was no constitutive production of IL-1 by these cells. However, synovial fluid mononuclear cells could be induced to secrete both IL-6 and IL-1 after stimulation with LPS. The LPS-responsive cells were monocytes and not lymphocytes or dendritic cells. These findings suggest that IL-6 is involved in inflammatory joint disease. However, the primary cells synthesizing it may be located in the synovial lining instead of the joint exudate.
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PMID:IL-6/IFN-beta 2 in synovial effusions of patients with rheumatoid arthritis and other arthritides. Identification of several isoforms and studies of cellular sources. 278 56

Sera from 53 patients, 26 with systemic lupus erythematosus (SLE), 8 with rheumatoid arthritis (RA), 9 with Sjogren's syndrome (SS), and 10 with scleroderma (Scl), were screened for the presence of antibodies against liver-type poly(A) polymerase and tumor-type poly(A) polymerase. Sixty percent of the patients with the above four autoimmune diseases have antibodies directed against liver poly(A) polymerase, whereas sera from 74% of the patients contained anti-hepatoma poly(A) polymerase antibodies. About 25% of the patients produced antibodies exclusively against the tumor poly(A) polymerase. IgG containing anti-liver or anti-tumor poly(A) polymerase antibodies inhibited the activity of the respective enzyme. IgG containing antibodies against liver and tumor enzymes inhibited the activity of both enzymes, whereas IgG from sera that did not react with poly(A) polymerase had no effect on either enzyme. These data demonstrated the specificity of these autoantibodies and confirmed the results of the radioimmunoassay.
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PMID:Antibodies against nuclear poly(A) polymerases in rheumatic autoimmune diseases. 303 Nov 26

Three human T-cell clones with activated killer activity (5B5, 5C1, and 7B5) which could lyse various tumor cell lines were established. The cytotoxic activity of these clones was decreased by incubation with anti-CD3 monoclonal antibody, suggesting that they recognized tumor cells by T-cell antigen receptor. A monoclonal antibody which blocked the cytotoxic activity of clone 5B5 was obtained. This antibody (N1977) blocked the binding and cytotoxic activity of clone 5B5 at the target cell level, suggesting that the antigen defined by N1977 antibody, designated as ATM-1, was a target molecule recognized by 5B5 cells. ATM-1 in the conditioned medium of a cancer cell line (NBT-2) and serum from a patient with lung cancer was characterized by following its immunoreactivity. On gel filtration, both the conditioned medium and the serum gave three peaks of ATM-1 immunoreactivity, corresponding to approximate molecular weights of 1,200,000, 700,000, and 120,000, respectively. They were chromatofocused at pH 4.0, 4.8, and 6.5, respectively. The high molecular weight forms were shown to be molecules with the disulfide-linked elementary glycoprotein with ATM-1 immunoreactivity and approximate molecular weight of 120,000. Most of the molecules with ATM-1 immunoreactivity bound to both concanavalin A and wheat germ agglutinin, and their binding activity to the antibodies was lost by treatment at 60 degrees C for 30 min. An assay of ATM-1 level in sera was performed by a sandwich enzyme immunoassay. The following positive percentages were obtained from preliminary clinical studies: breast cancer, 67% (8 of 12 cases); hepatocellular carcinoma, 83% (10 of 12 cases); gastric cancer, 58% (7 of 12 cases); lung cancer, 41% (5 of 12 cases); hematological malignancies, 0% (0 of 9 cases); systemic lupus erythematosus, 0% (0 of 8 cases); rheumatoid arthritis, 0% (0 of 8 cases).
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PMID:Identification of a tumor-associated target antigen, ATM-1, for a human T-cell clone with activated killer activity and its existence in sera of cancer patients. 304 79


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