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  • 1
    Keywords: tumor ; carcinoma ; DIAGNOSIS ; QUANTIFICATION ; EXPOSURE ; HEPATOCELLULAR-CARCINOMA ; liver ; RISK ; SITE ; GENE ; TUMORS ; PATIENT ; DNA ; INFECTION ; hepatocellular carcinoma ; PLASMA ; AGE ; MUTATION ; PROSTATE-CANCER ; ELECTROSPRAY ; mass spectrometry ; REGION ; MASS-SPECTROMETRY ; REGIONS ; RECRUITMENT ; INDIVIDUALS ; SELECTION ; QUANTITATIVE-ANALYSIS ; PREVALENCE ; MASSES ; STANDARD ; SUBSET ; P53 GENE ; targeted ; LEVEL ; AFLATOXIN EXPOSURE ; INTERVAL ; CODON ; analysis ; HEPATITIS-B ; GENDER ; MASS ; PARTICIPANTS ; AFLATOXIN B-1 ; CELL-FREE DNA ; CODON-249 MUTATIONS ; GAMBIA ; HEPATOCELLULAR-CARCINOMA PATIENTS ; WEST-AFRICA ; hepatitis B
    Abstract: A mutation in codon 249 of the TP53 gene (249(Ser)), related to aflatoxin B(1) exposure, has previously been associated with hepatocellular carcinoma risk. Using a novel internal standard plasmid, plasma concentrations of 249(Ser)-mutated DNA were quantified by electrospray ionization mass spectrometry in 89 hepatocellular carcinoma cases, 42 cirrhotic patients, and 131 nonliver diseased control subjects, all from highly aflatoxin-exposed regions of The Gambia. The hepatocellular carcinoma cases had higher median plasma concentrations of 249(Ser) (2,800 copies/mL; interquartile range: 500-11,000) compared with either cirrhotic (500 copies/mL; interquartile range: 500-2,600) or control subjects (500 copies/mL; interquartile range: 500-2,000; P 〈 0.05). About half (52%) of the hepatocellular carcinoma cases had 〉2,500 copies of 249(Ser)/mL plasma, corresponding to the prevalence of this mutation in liver tumors in The Gambia. In comparison, only 15% of control group and 26% of cirrhotic participants exceeded this level (P 〈 0.05). Further subset analysis revealed a statistically significant, quantitative relation between diagnosis of hepatocellular carcinoma and levels of 249(Ser) detected at 2,501 to 10,000 copies/mL plasma (odds ratio, 3.8; 95% confidence interval, 1.3-10.9) and at 〉10,000 copies/mL plasma (odds ratio, 62; 95% confidence interval, 4.7-820) when compared with control subjects and after adjusting for age, gender, recruitment site, hepatitis B and C serologic status, and total DNA concentration. Levels of 〉10,000 copies of 249(Ser)/mL plasma were also significantly associated with the diagnosis of hepatocellular carcinoma (odds ratio, 15; 95% confidence interval, 1.6-140) when compared with cirrhotic patients. Potential applications for the quantification of 249(Ser) DNA in plasma include estimation of long-term, cumulative aflatoxin exposure and selection of appropriate high-risk individuals for targeted intervention.
    Type of Publication: Journal article published
    PubMed ID: 16365016
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  • 2
    Keywords: SPECTRA ; BLOOD ; neoplasms ; CLASSIFICATION ; GENERATION ; RISK ; RNA ; PATIENT ; INFECTION ; LIVER-TRANSPLANTATION ; ASSOCIATION ; antibodies ; antibody ; virus ; NO ; LYMPHOMA ; MALIGNANCIES ; AGE ; etiology ; LYMPHOCYTES ; case-control studies ; PREVALENCE ; immunosuppression ; B-CELL LYMPHOMA ; HEMOPHILIA ; NON-HODGKINS-LYMPHOMA ; ELISA ; MALIGNANCY ; REGRESSION ; ASSOCIATIONS ; GRADE ; HCV ; hepatitis C ; LYMPHOPROLIFERATIVE DISORDERS ; MALIGNANT-LYMPHOMA ; MIXED CRYOGLOBULINEMIA ; REARRANGEMENT ; RECIPIENTS
    Abstract: Hepatitis C virus (HCV) has been implicated in the etiology of malignant lymphomas. We estimated the risk of lymphoma associated with detection of HCV infection. Cases (n = 529) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in 4 centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (n = 600) were hospitalized patients matched to the cases by 5-year age group, gender and study center. Several medical conditions associated with severe immunosuppression precluded the eligibility of controls. Patients underwent a personal interview and blood sampling. HCV positive subjects were considered those with antibody response to third generation ELISA or detection of HCV RNA with Amplicor 2.0. Cases were systematically tested for HIV antibodies. We used the chi(2) test and unconditional logistic regression to estimate the odds ratio (OR) and 95% confidence interval (95%. Cl) for lymphoma associated with HCV. HCV infection was detected in 40 cases (73%) and 23 (3.8%) control subjects. Six of 16 patients with HIV-related lymphomas and 4 of 8 organ-recipient-related lymphomas were HCV positive. The analysis, excluding HIV-infected subjects and organ recipients, led to a prevalence of HCV of 5.9% among cases and 3.8% among controls. The age-, gender- and center-adjusted OR for all lymphomas was 1.58 (95% Cl = 0.89-2.79). Among all lymphoma categories, HCV was associated with an increased risk of low grade B-cell lymphomas not otherwise specified (NOS) (OR = 35.98, 95% Cl = 4.70-275.4). A 2-fold excess risk associated to HCV was observed for marginal B-cell lymphomas, diffuse large B-cell lymphoma and lymphoma B NOS but the associations were not statistically significant. HCV infection is associated with an increased risk of a broad spectrum of lymphoid neoplasms among non severely immunocompromised subjects in Spain. (C) 2004 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15185347
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of epidemiology 1 (1985), S. 155-159 
    ISSN: 1573-7284
    Keywords: Retrovirus infections ; Immunologic deficiency syndromes ; Homosexuality ; Hemophilia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human T-lymphotropic virus type III (HTLV-III) is a recently discovered retrovirus with tropism and cytotoxicity for the OKT4+ lymphocytes that are depleted in the acquired immune deficiency syndrome (AIDS). In addition to the frequent detection of HTLV-III in patients with AIDS and related syndromes, seroepidemiological studies have shown that HTLV-III can be transmitted by sexual contact and blood transfusion in a manner identical to the putative AIDS agent. Analyses of stored sera have revealed that HTLV-III antibodies appeared in high-risk groups some two years before the disease outbreak, which corresponds to the apparent incubation period in patients with transfusion-associated AIDS. The risk of developing AIDS is clearly associated with HTLV-III seropositivity and may be as high as 20% within three years. Strong evidence that HTLV-III is the AIDS agent mandates aggressive efforts to minimize further sexual, maternal-fetal, and blood-borne transmission of this virus while pursuing vaccine development and antiretroviral therapies.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human ...
    Type of Medium: Electronic Resource
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