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Acute leukemia in Burkitt lymphoma.

Burkitt lymphoma uncommonly presents as a acute leukemia. We describe the clinical course and findings of a 14-year-old female with Burkitt lymphoma who presented with acute leukemia. splenomegaly and an abdominal mass. She responded initially to prednisone alone and later achieved full remission with combination chemotherapy. Established morphologic criteria and clinical course were consistent with the diagnosis of Burkitt lymphoma (1), although B-cell determinants were not present on her tumor cells.

Abdominal Neoplasms

B-cell leukemia-lymphoma with striking resemblance to Burkitt lymphoma in a 70-year-old woman.

A 70-year-old woman developed acute leukemia and a serum IgM spike. She entered complete remission with an adriamycin, vincristine, cytosine arabinoside, and prednisone combination. Bone marrow remission was maintained with intermittent cytosine arabinoside; however, she developed large skin nodules which partly remitted following adriamycin, vincristine, cyclophosphamide, and prednisone combination. They very rapidly recurred, and she died soon after. Autopsy revealed extensive tumor in the abdomen, pelvis, and thoracic cavity, but no bone marrow involvement. Histology revealed a "starry sky" appearance. Cytology showed undifferentiated cells with vacuolated cytoplasm resembling Burkitt lymphoma cells. Peroxidase and esterase stains were negative. There was strong pyroninophilia and the periodic acid-Schiff reaction showed granular activity in the cytoplasm. Electron microscopic appearances also resembled Burkitt lymphoma. Cytogenetic studies were normal, with no Ph1 chromosome. Immunofluorescence demonstrated surface IgM and a little IgA. 3H-thymidine incorporation was high, indicating rapid growth. Dibutyral cyclic adenosine monophosphate (cAMP) stimulated growth, which was further evidence of the lymphoid origin of the tumor. The close resemblance of this tumor to Burkitt lymphoma emphasizes the difficulties in systematically classifying the lymphomas.

Acute Disease

Pattern of hemoglobin concentration in untreated Burkitt lymphoma patients in Ibadan.

Hemoglobin concentration is studied in 128 untreated Burkitt lymphoma patients in Ibadan. While there is no significant diagnostic pattern in hemoglobin concentration, Burkitt lymphoma patients show marked anemia as compared with healthy adult Nigerians. The degree of involvement of malarial parasitemia in producing anemia in Burkitt lymphoma patients has yet to be determined.

Anemia

Isolation of a herpesvirus-specific DNA polymerase from tissues of an American patient with Burkitt lymphoma.

A DNA polymerase (DNA nucleotidyltransferase) has been partially purified from a neck mass of an American patient with Burkitt lymphoma and separated from the cellular DNA polymerases. The molecular weight of the enzyme was approximately 90,000. The enzyme differs from the cellular DNA polymerases, but resembles herpes-virus-induced DNA polymerase in its primer template preference, high monovalent cation requirement for activity, and sensitivity to phosphonoacetate. Enzyme activity was inhibited specifically by an antibody directed against herpes-simplex-virus-induced DNA polymerase but not by antibodies directed against DNA polymerase alpha of HeLa cells and DNA polymerase gamma of a normal human lymphoblast cell line, NC37. Although serum of the patient with Burkitt lymphoma contained high Epstein-Barr virus titer, addition of the serum to the assay mixture did not have any effect on the activity of Burkitt lymphoma DNA polymerase. Tissues from spleen and liver of the patient with Burkitt lymphoma did not contain the herpes-virus-induced DNA polymerase. Detection of the herpes virus polymerase in the Burkitt lymphoma tissue provides additional evidence for the association of Epstein-Barr virus with this malignancy.

Adult

Mode of integration of Epstein-Barr virus genome into host DNA in Burkitt lymphoma cells.

The ebv dna integrated into the host genome from cell of an African Burkitt lymphoma biopsy has been compared to the corresponding fraction of EBV DNA from the cell line SU-AmB-2 which is of American Burkitt lymphoma origin. It is shown that while, in the case of the African biopsy, large pieces of EBV DNA sequences are integrated into the host DNA, much smaller pieces of virus DNA are integrated into the DNA of the SU-AmB-2 cells. The possibility that this difference might be related to the fact that EBV is rarely associated with Burkitt lymphomas outside East Africa is discussed.

Biopsy

A novel interaction involving a polypeptide chain (P33) in covalent linkage with IgM on the surface of a Burkitt lymphoma cell line (Daudi).

The surface IgM of Daudi Burkitt lymphoma cells has been shown to consist of mu chains and kappa chains covalently linked, by disulfide bonding, to a novel polypeptide chain of approximate molecular weight 33,000. This novel polypeptide chain (P33) is similar in several properties to the heavy chain of the Ia antigen: glycoprotein nature; apparent molecular weight; isoelectric behavior and cysteine content. The linkage of P33 to surface immunoglobulin has not been observed with any other human lymphoma or lymphoblastoid cell lines.

Binding Sites

Ultrasound evaluation of American Burkitt's lymphoma.

Burkitt's lymphoma is a childhood disease that characteristically produces large, bulky abdominal tumors. Although these are potentially curable, chemotherapy can produce rapid tumor lysis, with subsequent life-threatening metabolic abnormalities, especially in those patients with large tumors or those who have compromised renal function. Twenty-two patients with proven Burkitt's lymphoma were evaluated by ultrasound. Thirteen patients had abdominal masses. These masses tended to be large, solitary, and acoustically homogeneous. Although most of these tumors were found in the pelvis, upper abdominal and retroperitoneal tumors were also encountered. None of the patients had the typical paravertebral mantle of enlarged nodes seen in other types of lymphoma. In 11 patients with abnormal intravenous pyelograms, ultrasound successfully distinguished between renal lymphoma, hydronephrosis, and, by exclusion, metabolic renal disease. The absence of lymph node disease and the presence of bulky homogeneous extranodal tumor are characteristic ultrasound findings in Burkitt's lymphoma. By locating and quantifying tumor mass and distinguishing between renal lymphoma and hydronephrosis, ultrasound proved to be clinically useful in the management of this disease.

Abdominal Neoplasms

Influence of mono- and multivalent cations on the electrokinetic properties of normal human lymphoid and burkitt lymphoma cells.

Various mono- and multivalent cations, at constant ionic strength, affected the surface electrokinetic properties of normal human lymphoid and Burkitt lymphoma cells in a manner which reflected more the physicochemical properties and binding affinities of the cation than its valence. The effect was expressed in the changes of the magnitude of the net surface charge and in the shift of the isoelectric point of the surface. These changes were greater at the surface of Burkitt's lymphoma cells than at the surface of their normal cell-line counterparts.

Binding Sites

Persistent herpes simplex virus infections established in two Burkitt lymphoma derived cell lines.

Examination of P3HR-I cells (Epstein-Barr virus [EBV] producer) persistently infected with the MAL strain of herpes simplex virus type I (HSV-I) suggested that only a few cells were actively producing a virus indistinguishable from HSV-I (MAL) despite the presence of immunofluorescent HSV-I antigens associated with the majority of cells. EBV-specific immunofluorescence was not altered in HSV-I persistently infected P3HR-I cells. HSV-I persistently infected cells, labelled for 72 h with 14C-thymidine, incorporated approx. 8% of the label into cell associated HSV-I DNA as resolved by caesium chloride gradients. Values greater than 8% of the total were suggested by hybridization of gradient fractions with 3H-HSV-I DNA. To determine whether the establishment of HSV persistent infections in Burkitt lymphoma derived cells was a general phenomenon, six strains of HSV-I (MAL, KOS, Patton, Syn R, BF and SYN V) and two strains of type 2 (333 and MS) were used to infect the P3HR-I and Raji (EBV non-producer) cell lines derived from Burkitt lymphomas. In P3HR-I cells, persistent infections were established with all strains of HSV-I but not with HSV-2. In Raji cells, persistent infections were established with all strains of HSV-I, except Syn V, and with both strains of HSV-2. No external support was required to maintain these infections.

Adsorption

Correlated expression of a B-lymphocyte-specific glycoprotein (gp27/35) and the EBV receptor/C3 receptor complex in sublines from the same Burkitt lymphoma.

A series of virus-producer and non-producer sublines, derived from the Burkitt lymphoma line Jijoye and its P3HR-1 clone, were previously found to differ in the expression of EBV receptors and, in parallel, C3 receptors. The differences could be related to an "internal selection" caused by the cytopathic P3HR-1 virus variant, favouring the growth of receptor-negative cells. We have now analyzed the same lines for the expression of a B-lymphocyte-specific glycoprotein (gp27/35). A close parallellism was found between the expression of the EBV receptor-complement receptor complex and the glycoprotein, measured by quantitative absorption. The results favour a relationship between gp27/35 and EBV/C3 receptor expression.

Antigen-Antibody Complex

Chromosomes and causation of human cancer and leukemia: XXXVI. The 14q+ anomaly in an American Burkitt lymphoma and its value in the definition of lymphoproliferative disorders.

A case of a 10-year-old boy with American Burkitt lymphoma is presented in whom a 14q+ due to t(8;14)(q23;q32) was shown to exist in the ascitic lymphoma cells. This appears to be the first demonstration of such a translocation in uncultured material. In addition, another translocation involving the X chromosome, hitherto not observed in Burkitt tumors, was demonstrated. The karyotypic findings have been related to the cytogenetic experience in Burkitt and other lymphomas, with emphasis being put on the importance of the 14q+ anomaly in lymphoproliferative diseases.

Burkitt Lymphoma

Burkitt lymphoma in an American infant under one year of age, with electron microscopic examination of the tumor.

Burkitt lymphoma in the United States has not been reported in a child under the age of one year. We report here a nine-month-old child who had facial involvement and a rapidly downhill course. This occurred despite an early response to combination chemotherapy and vigorous supportive measures. Electron microscopic examination of the tumor is also presented.

Antineoplastic Agents

The EBV-carrying, beta2M/HLA deficient Burkitt lymphoma line Daudi is sensitive to EBV-specific killer T-cells of mononucleosis patients.

The beta2-microglobulin/HLA deficient Burkitt lymphoma line Daudi was tested for sensitivity to EBV-specific cytotoxicity mediated by natural killer (NK)-depleted T-cells from acute mononucleosis patients. While the Daudi line was not as sensitive as the reference EBV-genome-positive target line, it was clearly sensitive in the majority of cases. This would speak against a major role of syngeneic restriction in this system.

Burkitt Lymphoma

Origin of lymphoid lines established from mixed cultures of cord-blood lymphocytes and explants from infectious mononucleosis, Burkitt lymphoma and healthy donors.

Lymphocytes were explanted from EBV-seropositive donors including peripheral blood of infectious mononucleosis patients, healthy donors and EBV-genome-carrying cells from Burkitt lymphoma (BL) biopsies or nude mouse-passaged, BL-biopsy-derived lines. The explanted cells were mixed with fresh cord-blood lymphocytes from mice of the opposite sex. In all categories of derived lines, cord-blood cell progeny was predominant, as judged by the sex marker and other associated markers. Only one BL biopsy line, serially passaged in nude mice, gave rise to a monoclonal lymphoma line.

Animals

Attempts to demonstrate virus-specific sequences in human tumors. IV. EB viral DNA in European Burkitt lymphoma and immunoblastic lymphadenopathy with excessive plasmacytosis.

Various biopsies from different European malignant lymphomas, two biopsies from nasopharyngeal carcinomas, and material from non-neoplastic lymph nodes were assayed for the presence of Epstein-Barr virus (EBV) DNA by nucleic acid hybridization. Reassociation kinetics of in vitro-labelled EBV DNA were studied in the presence of tumor DNA. The lymphomas tested included among others follicular lymphomas, germinocytomas, immunoblastic lymphomas and lymphoplasmacytoid immunocytomas. Epstein-Barr viral DNA was demonstrated within the two nasopharyngeal carcinoma biopsies as expected. A histologically typical Burkitt lymphoma as well as an immunoblastic lymphadenopathy with excessive plasmacytosis also contained EBV-DNA. The Burkitt biopsy revealed about 15 EBV genome equivalents per cell. Antibodies against EBV-specific antigens were highly elevated in the serum of this patient. The material of the patient with immunoblastic lymphadenopathy contained 2-3 EBV genome equivalents per cell.

Aged

Biological properties and viral surface antigens of Burkitt lymphoma- and mononucleosis- derived strains of Epstein-Barr virus released from transformed marmoset cells.

Three strains of Epstein-Barr virus (EBV), two from Burkitt lymphoma (BL) and one from infectious mononucleosis (IM) were used to transform separate cultures of the same batch of primary marmoset leukocytes, and the viruses released from the transformants were compared. The three viruses shared properties of the transforming biotype of EBV, namely, stimulation of DNA synthesis and immortalization of cord blood leukocytes, and failure to induce "early antigen" in lymphoblast lines. All viruses produced more virus in transformed marmoset cells than in transformed human cells, as measured by the number of EBV genomes detected by complementary RNA/DNA hybridization, by virus capsid antigen expression, or by released virions and biologically active virus. Reference human sera and sera from primary EBV infections were used to compare the three virus strains in a virus neutralization test based on inhibition of stimulation of DNA synthesis. Specimens taken late in convalescence from patients with mononucleosis and sera from marmosets experimentally infected with virus from a patient with mononucleosis neutralized the homologous virus, as well as the two virus strains isolated from patients with BL. This finding indicates that viral antigens that elicit neutralizing antibodies are shared among the strains. However, in certain sera the neutralizing-antibody titer against one strain was consistently higher than against another strain. Furthermore, sera taken early after onset of IM contained low levels of neutralizing antibody against IM-derived virus, but failed to neutralize BL-derived virus. These latter findings suggest the existence of heterogeneity among surface antigens of EBVs. The results emphasize the biological and antigenic similarity of EBV isolates from BL and IM and do not suggest major subtype variations. It remains to be determined whether antigenic diversity such as described or virus genome variation detectable by other means is epidemiologically significant.

Animals

An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection.

An in vitro line was derived from an American Burkitt lymphoma, designated Ra No. 1, which produced malignant tumors when inoculated into thymus-deficient nude mice. The cells have B-lymphocyte characteristics, with surface-associated mu and kappa chains and Epstein-Barr virus (EBV) receptors, and can be readily infected with EBV in vitro. B95-8 virus induced EBV-determined nuclear antigen (EBNA) but not early antigen (EA) in Ra No. 1 cells, whereas P3HR-1 virus induced both EBNA and EA, but the EA level was much lower than in the prototype Raji strain, EBNA and EA levels were comparable in Ra No. 1 and in the previously established, EBV-infection-sensitive BJA-B lymphoma. The two lines differed, however, because BJA-B could be converted into a permanent EBV-carrying line by the B95-8 but not by the P3HR-1 virus strain, whereas Ra No. 1 could be converted by the P3HR-1 virus. This demonstrates that different B-lymphocyte-derived lymphoma lines can vary with regard to the restrictive control they can exert on the same virus strain. Furthermore, virus strains vary in their sensitivity to the restrictions of the same host cell. Permanent EBV conversion of the Ra No. 1 cell did not appear to change the cellular controls, as judged by the unchanged sensitivity of the cell to viral antigen (EA, viral capsid antigen) induction by P3HR-1 virus superinfection.

Animals