Passing on the miracle of life to native Hawaiian children.
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Biomedical subjects
Publications and source records attributed to J Luka.
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Patients with Hodgkin's disease (HD) frequently show elevated serum titers against human herpersvirus-6 (HHV-6) and their tissues contain significantly increased numbers of cells with HHV-6 DNA. This may coincide with similar data of Epstein-Barr virus (EBV) infections. According to in vitro studies, Hodgkin- and Reed-Sternberg (RS) cells can be infected by HHV-6 and may be coinfected by HHV-6 and EBV. Both viruses are potentially oncogenic and also may interfere with the production of various cytokines. We now demonstrate by using immunohistological methods that HHV-6 antigens are present in 77.3% of the HD lymphomas, 37% of which contain the replication-associated p41 "early-late" antigen and 63% the late membrane antigen complex gp116/64/54. Monocytic cell populations including HD and RS cells are most frequently antigen-positive, while lymphoid cells are less frequently. These cells also express IL-6 and IL-6 receptors as well as the IL-2 receptor a chain (CD25), while only occasionally the IL-2 receptor beta chain (p70). IL-6 receptors are significantly more frequently expressed than IL-6 itself. HD and RS cells constitute a significant pool of proliferating cells as reflected by their 95% positivity for PCNA, yet tumor suppressor genes are found in only 21% and the proto-oncogenes fes and met are expressed in various types of cells. The data may indicate that both viruses possibly contribute to the course of the disease through polyclonal stimulations of cell proliferation and coincident dysregulation of the cytokine network control of cell function and proliferation. A direct oncogenic effect of EBV and HHV-6 in HD appears less probable.
Fifty patients with various hyperplastic and malignant lymphoproliferative diseases were investigated for evidence of human herpesvirus-6 infection. Virus DNA and antigen expression was investigated in lymph node biopsies by in situ hybridization and immunohistology and was correlated with data of immunophenotyping. Supplemental immunoglobulin- and T cell receptor gene rearrangement studies were used to support the classification of the proliferative lymphoid lesion. Elevated numbers of cells carrying HHV-6 DNA and/or antigens were found in cases of Hodgkin's lymphoma and follicular center cell non-Hodgkin's lymphoma as well as atypical polyclonal lymphoproliferation (APL), yet not in reactive lymphoid hyperplasia and in most other lymphomas. Immunophenotyping showed that virus -infected cells were primarily lympho-histiocytic elements, less frequently Hodgkin's- and Reed-Sternberg cells, and not malignant B lymphocytes as in follicular center cell lymphomas. This suggests that the virus is rather not the causative oncogen in these cases, yet does not exclude a cocarcinogenic effect of it during the development and ths course of uncontrolled lymphoproliferation.
DNA from Epstein-Barr virus (EBV) Types A, B and Herpesvirus-6 (HHV-6) Variants A and B was detected by the Polymerase chain reaction (PCR) in the saliva of 51 non-immunocompromised donor patients and in the blood of seventy non-immunocompromised donor patients with specific signs and symptoms. The minimum selection criteria for each patient included acute or recurrent upper respiratory infection, unilateral thoracolumbar muscle spasm and fatigue. PCR DNA detection in the saliva of selected donors revealed 80% of the donors had either Type A or B EBV (41 of 51), 34.1% Type B EBV only (14 of 41), 9% Type A only (4 of 41), and 56.1% Type A and B EBV (23 of 41). HHV-6 DNA was detected in 45.0% (23 of 51). PCR for EBV in blood of selected donors revealed 68.5% Type A or B EBV (48 of 70), 0% type B EBV alone, 64.8% Type A EBV only (31 of 48) and 35.4% both Type A and B EBV (17 of 48). HHV-6 was detected in 96.4% (64 of 70). The association of Type B EBV in the pathogenesis of these patients is explored based on the PCR quantitation of B type EBV DNA present in the samples.