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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 1,225 records · Page 68Linked to original sources

Direct evidence for the presence of Epstein-Barr virus DNA and nuclear antigen in malignant epithelial cells from patients with poorly differentiated carcinoma of the nasopharynx.

A well-differentiated squamous cell carcinoma and three poorly differentiated carcinomas of the nasopharynx were analyzed for the presence of Epstein-Barr virus DNA by hybridization with radioactive complementary RNA. The well-differentiated carcinoma contained no detectable Epstein-Barr virus DNA, whereas the three anaplastic carcinomas contained 41, 16, and 14 viral genome equivalents per cell. The anaplastic carcinomas were heavily infiltrated with lymphocytes and other non-neoplastic cells. All four tumors were successfully passaged in nude (thymusless) mice. Mouse cell admixture in the heterotransplanted tumors was estimated by analysis of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and varied between 25% and 80%. After two passages in nude mice, the carcinoma that was negative for Epstein-Barr virus DNA remained negative, while the three anaplastic carcinomas retained their viral DNA. After correction for mouse cell admixture, the latter tumors were found to contain about 80, 55, and 160 Epstein-Barr virus genome equivalents per human cell. The virus-determined nuclear antigen was localized in the large carcinoma cell clusters in all three mouse-passaged tumors positive for the viral DNA, but other virus-determined antigens were not detected, indicating the absence of virus induction. In contrast to the original tumor biopsies, the nude-mouse-passaged tumors showed virtually no lymphocytic infiltration. It is concluded that the Epstein-Barr virus DNA found in biopsies of human nasopharyngeal carcinomas is localized in the neoplastic cells.

Animals↗

Human leukemia-associated anti-nuclear reactivity.

A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological specificity and morphological appearance, although it is visualized by the same method. Serum from acute myeloid leukemia patients gave positive reactions in 73% of the cases. In acute lymphatic leukemia, chronic myeloid leukemia, chronic lymphatic leukemia, and Burkitt's lymphoma the sera were positive in 35, 14, 19, and 24%, respectively. Two of five polycythemia and two of eleven myeloma sera were also positive. Among 61 healthy controls, 58 were negative, whereas three showed a diffuse nuclear staining with a different pattern. Among 24 carcinoma patients, 18 were negative, whereas six gave a nuclear staining with a different, diffuse pattern. Sera from 20 patients who had recovered from infectious mononucleosis were all negative. In addition to the blasts of acute myeloid leukemia, a similar reactivity was seen with two Epstein-Barr virus DNA and EBNA-negative African lymphoma biopsies and in a short-lived tissue culture line derived from one of them. LANA could be a fetal or tissue-specific antigen, a virally determined antigen, or a specific form of anti-nuclear reactivity.

Antibodies, Antinuclear↗

Epstein-Barr virus-associated membrane-reactive antibodies during long term survival Burkitt's lymphoma.

Antibodies to Epstein-Barr virus associated cell membrane antigens persisted or slowly decreased during prolonged uncomplicated survival of patients with Burkitt's lymphoma in remission. Serum was sampled from four patients within 6 months before recurrence occurring after the first year and preceded by remission during more than 6 months. Rapid and significant decreases of the antibodies before clinical recognition of the recurrences were found in three patients. The fourth patient had slowly increasing titers before relapse. Immune stimulant treatment during remission, with BCG (Bacille Calmette Guérin vaccine) or BCG + Bordetella pertussis, temporarily increased the antibody levels. Possible mechanisms for the observed titer changes before recurrence are discussed.

Antibodies, Viral↗

Continuous lymphoid cell lines with characteristics of B cells (bone-marrow-derived), lacking the Epstein-Barr virus genome and derived from three human lymphomas.

Three exceptional cell lines have been tested for the presence of the Epstein-Barr virus genome by nucleic acid hybridization (complementary RNA.DNA) and Epstein-Barr virus-determined nuclear antigen tests. Two lines were derived from Swedish lymphoma cases and one from an African Burkitt-like lymphoma biopsy that was negative for Epstein-Barr virus DNA and the virus-determined nuclear antigen. All three lines apparently lacked the viral genome. Two of the three lines clearly had characteristics of B-cells (bone-marrow-derived).

Antigens, Viral↗

Infection of EBV-genome-negative and -positive human lymphoblastoid cell lines with biologically different preparations of EBV.

Epstein-Barr virus (EBV) derived from the B95-8 line has transforming activity for cord blood cells, whereas virus derived from the P3HR-1 line lacks such activity. When the two viral preparations were compared for their ability to infect the same EBV-genome-negative lymphoblastoid cell line, BJA-B, they induced approximately the same number of EBV-determined nuclear antigen (EBNA)-positive cells. EBNA is compatibile with continued cell proliferation. No early antigen (EA)-positive cells appeared in the B95-8 virus-infected cultures, whereas P3HR-1 virus-infected cells went on to express EA. EA signals the entry of the cell into the lytic cycle. No late viral antigen (VCA) appeared and, as a consequence, the P3HR-1 virus infection became abortive. In contrast, the EBNA-positive cells induced by the B95-8 virus continued to divide over several weeks. These findings show that different EBV isolates may differ in their biological activity, probably due to their having different degrees of viral dependence on restrictive host cell controls.

Antigens, Viral↗