Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha1-fetoprotein (AFP) is an alpha1-glycoprotein which can be found in high concentration during fetal development in many mammals, birds, sharks and, also, man. The alpha-fetoproteins of various species have similar physico-chemical properties and often common antigenic determinants. Differences of microheterogeneity depend on a different content of sialin-acid. During human fetal development the serum AFP concentration falls with increasing gestational age. 4-5 weeks after birth AFP can be detected usually in low serum concentrations. Using more sensitive immunulogic techniques e.g. radioimmunoassay there was shown that AFP is present in sera of normal adults in concentrations of 10-20 ng/ml. AFP serum concentrations rise physiologically during pregnancy up to 500-550 ng/ml. During fetal development liver, yolk sac and gastrointestinal tract are the major sites of synthesis. In primary liver cell carcinoma, hepatoblastoma and in teratoblastoma containing yolk sac tissue AFP synthesis rises in tumor cells; the AFP serum concentration increases above 2 microgram/ml. In patients with benign liver diseases e.g. virus hepatitis, a transient rise of AFP serum concentrations was seen. Moreover, increased levels of AFP were found in hereditary diseases e.g. congenital tyrosinemia, ataxia-telangiectasia and in the amniotic fluid in congenital nephrosis of Finnish type. AFP assay in serum is clinically important for the control of course and treatment of primary liver cell carcinoma and teratoblastoma. AFP assay in amniotic fluid is a method for the prenatal detection of neural tube defects and the fetal distress syndrome, especially.
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PMID:[Alpha1-fetoprotein: physiology, pathology and diagnosis especially in childhood (author's transl)]. 7 May 46

Ataxia-telangiectasia (AT) is a multi-system disease involving the cerebellum, cutaneous blood vessels and the immune system including both cellular and humoral components. It also involves hematological, endocrine and peripheral nervous systems. This disease is often associated with abnormal liver function tests, such as, raised alkaline phosphatase and various nonspecific histological changes in the liver. High incidence of various malignancies involving lymphoreticular, gastrointestinal and mesenchymal organs have reported in ataxia-telangiectasia. Elevated levels of alpha fetoprotein have been noted commonly in this disorder. In spite of the hepatic histological and biochemical changes associated with elevated alpha fetoprotein, to our knowledge, development of hepatocellular carcinoma has not been reported in patients with ataxia-telangiectasia. A case of a young white female with AT who developed hepatocellular carcinoma along with significantly elevated levels of alpha fetoprotein is presented.
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PMID:Ataxia-telangiectasia and hepatocellular carcinoma. 9 92

Radioligand binding studies were undertaken to establish the expression of angiotensin II (AII) receptors on the human hepatoma cell line, PLC-PRF-5. Cell membranes were shown to express a large number of AII receptors with high and low affinity binding sites having Bmax values of 1269 +/- 365 and 4190 +/- 1055 fmol/mg protein and affinities (Kd) of 2.0 +/- 0.3 nM and 8.7 +/- 0.4 nM, respectively. In intact cells a single class of AII binding site was seen with an affinity (Kd) of 6.7 +/- 1 nM and a Bmax value of 315 +/- 32 fmol/mg. In both membranes and intact cells AII, AIII and the selective angiotensin AT1 receptor antagonist, DuP 753, all had a high affinity for the receptor (Ki values in the nanomolar range), but the selective angiotensin AT2 ligands, PD 123177 and p-aminophenylalanine6 AII, had low affinity (Ki values in the micromolar range). These results indicate that the PLC-PRF-5 cells express the angiotensin AT1 receptor subtype. This was further supported by the demonstration of the sensitivity of the receptor to dithiothreitol (DTT). Pretreatment of membranes with DTT reduced [3H]AII binding in a concentration-dependent manner with an IC50 of 4.2 +/- 0.9 mM. The coupling of the AT1 receptor to signal transduction pathways was investigated. In intact cells AII (100 nM) evoked an increase in intracellular calcium ([Ca2+]i). This increase in [Ca2+]i was unaffected by PD 123177 (100 microM) but was abolished by DuP 753 (100 microM). Furthermore, AII (100 nM) did not inhibit forskolin (0.1-10 microM) stimulated cyclic AMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the angiotensin II receptor expressed by the human hepatoma cell line, PLC-PRF-5. 133 15

Although only a single gene exists for alpha-fetoprotein (AFP), differential glycosylation generates several different forms and these are associated with different tissues of origin, namely, liver, gastrointestinal tract, and yolk sac. This microheterogeneity of serum AFP was studied in seven patients with ataxia-telangiectasia (AT) in order to determine the tissue of origin of their elevated AFP levels. Concanavalin A (Con A), Lens culinaris agglutinin A (LCA-A), and erythroagglutinating phytohemagglutinin (E-PHA) affinity electrophoresis and antibody-affinity blotting were used to fractionate AFP. It was found that serum AFP in AT patients was composed mainly of Con-A band 2 (AFP-C2), LCA-A band 1 (AFP-L1), and E-PHA band 2 (AFP-P2). This profile of AFP species in AT patients is similar to those seen in neonates and patients with chronic hepatitis, but clearly different from AFP originating in hepatocellular carcinoma, gastric carcinoma, and yolk sac tumour cells. These data are compatible with a hepatic origin for the elevated AFP in AT patients. Since no evidence exists for ongoing liver damage in these patients, we suggest that the AFP gene in the AT liver may be under aberrant transcriptional control, perhaps secondary to a defect of DNA regulatory proteins which are necessary for hepatic maturation.
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PMID:Tissue of origin of elevated alpha-fetoprotein in ataxia-telangiectasia. 245 78

We studied a case of familial ataxia-telangiectasia in a 15-year-old girl who had a clinical history of cerebellar ataxia and recurrent pulmonary infections. She was found at autopsy to have a hepatocellular carcinoma, which has been described twice previously in the literature as occurring with this disorder. Family studies on the majority of her seven siblings (the product of one father and two mothers who were identical twins) showed one brother to have classic features of cerebellar ataxia, IgA deficiency, markedly elevated alpha-fetoprotein levels, and characteristic chromosomal abnormalities. This boy also died later of hepatocellular carcinoma in 1984. An affected sister had previously died of a respiratory tract infection.
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PMID:Ataxia telangiectasia with hepatocellular carcinoma in a 15-year-old girl and studies of her kindred. 299 58

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

The clinical manifestations, immunological, chromosomal, and multimodal electrophysiological studies of five Chinese patients with ataxia telangiectasia are described. One died of hepatocellular carcinoma not associated with Hepatitis B-antigenaemia. Another died of respiratory failure. Two siblings are free of sinopulmonary infections although they are wheelchair bound. Computed tomography of the brain showed cerebellar atrophy in four cases. Nerve conduction studies showed evidence of axonal neuropathy in all cases with the earliest detection at six years. Electromyography showed mild denervation changes in two cases. Two patients had abnormal somatosensory evoked potentials and one had abnormal visual and brain stem auditory evoked potentials. The level of alpha foetal protein was elevated whereas the serum carcino-embryonic antigen was normal in all patients.
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PMID:Ataxia telangiectasia in Chinese children. A clinical and electrophysiological study. 366 86

This editorial calls for development of quantitative assays for alpha fetoprotein (AFP) which incorporate a long-overdue uniform international standard for AFP. Statistics for presently available detection techniques are reviewed; Double-gel diffusion detects serum AFP in 1/3 white hepatoma patients and 1/3 embryonal gonadal teratoblastomas. Counterimmunoelectophoresis and electroimmunodiffusion detect AFP in more than 50% of white patients with hepatoma and a higher percentage of other racial groups. Sensitive radioimmunoassays (RIAs) can detect AFP in 85-95% of hepatoma patients; the other 5-15% are considered at present not to have AFP-producing tumors. RIAs also discern AFP in 2 other conditions; 1) gastrointestinal tract tumors and entodermally derived tumors; and 2) acute viral hepatitis. AFP in newborns is usually 1-5 mg/100 ml of blood. This level decreases (half-life, 3-5 days) during neonatancy to undetectable levels. AFP is elevated in children with 3 conditions: 1) hepatocellular carcinoma of hepatoblastoma; 2) gonadal teratoblastomas or embryonal carcinoma; and 3) ataxia telangiectasia, but not in other immune deficiency diseases. During gestation, fetal serum AFP reaches a 200-400 mg/100 ml of blood peak in the first trimester which drops to less than 5 mg/100 in newborn unbilical blood. Elevated maternal serum AFP has been shown to mark fetal distress and other pregnancy complications; these amounts are measured in nanorams and require sensitivity.
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PMID:Editorial: Alpha 1-fetoprotein: need for quantitative assays. 412 24

This paper reports the occurrence of renal cell carcinoma, hepatoma and malignant hepatic mixed tumor in a 22-year-old male with ataxia-telangiectasia (AT). Incidence of various malignant neoplasms is high in the patients with AT. The majority of these are lymphoreticular tumors and leukemia, and epithelial tumors are rare. This report is the first case with renal cell carcinoma and the second with hepatoma. The reason for a low incidence of epithelial tumors in AT is still obscure. It is possible that as the result of abnormal aging the tumors expected in the aged will occur in longer survivors with AT.
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PMID:Ataxia-telangiectasia with renal cell carcinoma and hepatoma. 625 35

We tested for infection with hepatitis C virus (HCV) in 58 patients affected by humoral immunodeficiencies: 43 common variable immunodeficiency (CVI), two hyper IgM syndrome (HIM), two IgG subclass deficiency, four ataxia-telangiectasia (AT), and seven X-linked agammaglobulinaemia (XLA). While the assessment of serum specific HCV antibodies in some of these patients was not informative because of the impairment in specific antibody production, the reverse transcriptase polymerase chain reaction (RT-PCR) assay used to detect serum HCV RNA was a useful method for diagnosing infection. We found that 38% of late onset hypogammaglobulinaemic patients (CVI, HIM or IgG subclass deficiency) had evidence of HCV infection. HCV infection was not detectable in patients with XLA or AT. The majority of our patients had persistent viraemia, and those who underwent liver biopsy showed histological findings of chronic hepatitis. Moreover, we could demonstrate in vitro that eight of 18 HCV-infected patients were actively producing anti-HCV antibodies, despite their impaired antibody production. The high rate of HCV infection in hypogammaglobulinaemic patients could be related to several nosocomial routes of transmission, including intravenous immune globulin administration. Despite the persistent viremia only two patients had cirrhosis and none had hepatocarcinoma.
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PMID:HCV infection in patients with primary defects of immunoglobulin production. 755 76


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