Abstract:
A screening program was developed to systematically look for evidence of retroviral involvement in human hematopathologies and neurological disorders. Utilizing nucleic acid hybridization assays, fresh and cultured tissue samples from biopsy and autopsy were screened for DNA sequences complementary to characterized DNA probes corresponding to human T-cell leukemia/lymphoma virus (HTLV) types I and II. Concomitant with the clinical survey was the implementation, assessment, and comparison with standard protocols of the novel in vitro gene amplification technique, polymerase chain reaction (PCR), for the detection of viral sequences present at low copy number. In conjunction with the DNA screening, radioimmunoprecipitation (RIP) assays were performed on patient (pt) sera samples to corroborate findings, determine patterns of antigen expression, and assess exposure to risk group populations. Evidence of retroviral involvement was found in the following diseases: smoldering and acute adult T-cell leukemia; adult T-cell lymphoma; immature and mature benign T-cell lymphocytoses; acute T-cell lymphoblastic leukemia; chronic myelogenous leukemia; and noncompressive myelopathy (NCM). HTLV-I was detected by PCR in both the peripheral blood and cerebral spinal fluid of NCM pts. This is the first finding of HTLV-I-hybridizing sequences in these pts. RIP analyses of NCM pt sera revealed strong reactivities against all of the HTLV-I proteins. Evidence of retroviral infection was also obtained by serological analyses in a substantial percentage (5-10%) of healthy iv drug abusers. Two HTLV-I-associated benign lymphocytosis cases were chosen for more detailed analyses. One of the cases consisted of a persistent polyclonal T-lymphocytosis that evolved into a lymphoma. The structure and expression of the associated provirus was examined in T-cell lines established from the pt's peripheral blood. The pt died of an opportunistic infection following chemotherapy, but at autopsy was free of tumor. No virus could be detected by conventional means. Using gene amplification technology, I was able to detect proviral DNA from HTLV-I and HIV in this pt's lymphoid tissues. There was no correlation of expression of the trans-activating gene, pX, of HTLV-I with type or stage of disease. These studies do not support the hypothesis that the pX protein is sufficient to cause malignant transformation. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No: AAD88-06684)
Keywords: Cross-Sectional Studies *DNA Probes Gene Amplification Human HTLV-I/*GENETICS HTLV-I Infections/*EPIDEMIOLOGY HTLV-II/*GENETICS HTLV-II Infections/*EPIDEMIOLOGY Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/EPIDEMIOLOGY *Mass Screening Risk Factors United States THESIS
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