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D T Purtilo

Publications and source records attributed to D T Purtilo.

At least 91 records · Page 5Linked to original sources
PubMed1987

Intermediate lymphocytic lymphoma: immunophenotypic and cytogenetic findings.

A detailed immunohistologic and cytogenetic analysis of 12 cases of intermediate lymphocytic lymphoma was performed. The characteristic immunophenotype of intermediate lymphocytic lymphoma was: surface IgM and IgD+, BA1+, B1+, BA2-, B2-, B4+, Leu 14+, Leu 1+, HLA-DR+, and common acute lymphocytic leukemia associated (CALLA) antigen negative. Clonal chromosome abnormalities were identified in ten cases, with structural or numerical abnormalities of chromosomes 11 or 12 in nine cases. Five cases had structural abnormalities involving the long arm of chromosome 11; three of these had translocations with chromosome 14 at band q32. Three cases had trisomy 12, and one case had a translocation involving the long arm of chromosome 12. The tenth case had a translocation involving the long arms of chromosomes 7 and 9. These characteristic immunophenotypic and cytogenetic findings suggest a close lineage relationship between intermediate lymphocytic lymphoma and small lymphocytic (well differentiated) lymphoma/chronic lymphocytic leukemia. Their differing clinical, cytologic, and architectural features suggest, however, that intermediate lymphocytic lymphoma should be considered a separate category of lymphocytic lymphoma in the International Working Formulation.

Biopsy↗
PubMed1987

Fatal infectious mononucleosis and virus-associated hemophagocytic syndrome.

A detailed clinicopathologic analysis of 52 cases of fatal infectious mononucleosis was performed. Fever, rash, generalized lymphadenopathy, hepatosplenomegaly, and blood cytopenias were the characteristic findings. Epstein-Barr virus infection was documented in 44 of the 52 patients. A triphasic process evolved in the blood and bone marrow of 43 patients. Early, the leukocyte count was elevated due to numerous atypical lymphoid cells, and the marrow was hyperplastic. Later, severe pancytopenia developed, and the marrow showed extensive infiltration by lymphoid cells with cellular necrosis and histiocytic hemophagocytosis. Terminally, the marrow showed massive necrosis with severe cellular depletion and marked histiocytic hemophagocytosis. The median survival time of the patients was six weeks. Opportunistic infections and/or acute hemorrhage were the major causes of death. We conclude that bone marrow damage secondary to an Epstein-Barr virus-associated hemophagocytic syndrome plays a major role in the death of patients with infectious mononucleosis.

Adolescent↗
PubMed1986

Sensitive assay for neutralizing antibodies against AIDS-related viruses (HTLV-III/LAV).

A sensitive assay for neutralizing antibodies (NA) against AIDS-related viruses (HTLV-III and LAV) was developed, using human T-cell lymphotropic virus type-I (HTLV-I)-bearing and HTLV-III-susceptible MT-4 cells. NA to HTLV-III in 21 patients with acquired immune deficiency syndrome (AIDS), 10 individuals with AIDS-related complex (ARC), 20 healthy male homosexuals, and 10 healthy male controls were titrated. Antibodies to HTLV-III were also detected by indirect immunofluorescence (IF). The assay was sensitive up to a dilution of 1:10 000. Sera from patients with AIDS showed a geometric mean titer (GMT) of NA of 1:475, whereas much higher GMTs (1:1318 and 1:1009) were observed in patients with ARC and healthy male homosexuals, respectively. Moreover, titers of NA significantly correlated with the levels of anti-HTLV-III antibodies detected by IF.

Antibodies, Viral↗
PubMed1986

Cystic fibrosis complicated by acute leukemia.

During a 3-month period, two men ages 20 and 25 years, respectively, with cystic fibrosis developed acute lymphocytic and nonlymphocytic leukemias, respectively. These two patients were among 120 patients who attended our cystic fibrosis clinic during the last 3 years. Thirty-five of the 120 patients have survived beyond the second decade. The authors ask whether acute leukemia will be recognized with increasing frequency in cystic fibrosis patients who achieve prolonged survival.

Adult↗
PubMed1986

Defective natural killing activity but retention of lymphocyte-mediated antibody-dependent cellular cytotoxicity in patients with the X-linked lymphoproliferative syndrome.

Cellular mediated immune responses in vitro of six males with X-linked lymphoproliferative syndrome (XLP) were investigated. Impaired natural killing (NK) activity compared to seven controls (P less than 0.001) and interferon-alpha activation (P less than 0.011) were detected. However, normal numbers of lymphocytes expressing NK-associated antigens (Leu-7 and MO1) and large granular lymphocytes (LGL) were observed in all patients. Normal lymphocyte-mediated antibody-dependent cellular cytotoxicity (ADCC) (P less than 0.531) was found. NK and ADCC activities have been regarded as being mediated by the same subsets of lymphocytes, however, results of this study do not support this hypothesis: lymphocytes with impaired NK but normal ADCC functions (NK-/K+) were found in males with XLP.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Pulmonary angiitis with atypical lymphoreticular infiltrates in Wiskott-Aldrich syndrome: possible relationship of lymphomatoid granulomatosis and EBV infection.

We describe a 12-year-old boy with Wiskott-Aldrich syndrome who developed a pulmonary vasculitis associated with lymphoreticular proliferation, consistent with the histological and clinical diagnosis of lymphomatoid granulomatosis. The lesions were responsive to cyclophosphamide and steroids. The patient has had severely depressed immune function and was shown to have abnormal Epstein-Barr virus (EBV)-specific cellular and humoral immune responses. Lymph nodes obtained at autopsy were positive for EBV genome. In this patient, reactivated EBV infection resulting from impaired immune surveillance of the virus may have been responsible for the development of this paraneoplastic disorder.

Child↗
PubMed1986

In-vitro infection of chronic lymphocytic leukemia cells by Epstein-Barr virus (EBV).

We sought to determine the potential of infecting lymphoid cells from patients with chronic leukemia (CLL) with Epstein-Barr virus (EBV) by testing for EBV receptors (EBVR) by flow cytometry, assessing for infectability of these cells by culturing with B95-8-derived virus, and staining for EB nuclear-associated antigens (EBNA) at various times post-infection. EBVR were present on 54-91% of lymphoid cells in seven cases of CLL and on 46% of prolymphocytic leukemia cells. Dynamic changes regarding EBNA positivity, morphology, and viability occurred post-infection with the virus. On day 2 only a few EBNA-positive lymphoblasts were observed. On days 11-21 positivity increased from 2 to 34% of cells. Simultaneously, the viable cell number declined to approximately 1/10th of original number. A significant proportion of the EBNA-positive cells corresponded to the original CLL cells. In 3 of 7 cases of CLL a Pan T-cell phenotype was demonstrated by Leu-1 monoclonal antibody testing. The infected cells did not react with two monoclonal antibodies, EBV-CS 1 and 4, which react with B-cell lymphoblastoid cell lines (B-LCL). Moreover, the B-LCL derived at 1-2 months post-infection of CLL cells did not express the Leu-1 antigen, but expressed EBV-CS 1 or 4 defined antigens. In the prolymphocytic leukemia, 64% of the cells showed EBNA positivity on day 7 and giant cells with huge round or multiple nuclei appeared which were EBNA-positive. CLL and prolymphocytic leukemia cells can be infected as demonstrated by EBNA-positivity. This infection does not lead to immediate transformation, but evokes lymphoblast and multinucleated giant cell production prior to the death of cells.

Aged↗
PubMed1986

Anti-Epstein-Barr virus memory T-cell response in Chediak-Higashi syndrome patients.

Memory cytotoxic T-cell responses to Epstein-Barr virus transformed B cells were studied in two EBV seropositive Chediak-Higashi syndrome patients who were manifesting the terminal lymphoproliferative stage of the syndrome. The number of cells required for 50% regression of EBV-infected autologous lymphoblastoid cell lines was similar to that in the parents and healthy subjects. This indicates adequate memory cytotoxic T-cell control of EBV-infected B lymphocytes. Defective mechanisms other than those mediated by circulating cytotoxic cells, might be responsible for the chronic active EBV infection observed in these patients.

B-Lymphocytes↗
PubMed1986

Cytogenetic abnormalities in noncutaneous peripheral T-cell lymphoma.

Cytogenetic studies were performed on lymph nodes from eight patients with noncutaneous peripheral T-cell lymphoma. At least one chromosomally abnormal clone was identified in each patient. Chromosomes having structural abnormalities in two or more patients included chromosome #1 (four), chromosome #2 (three), chromosome #4 (two), chromosome #8 (two), chromosome #14 (two), and chromosome #17 (two). The abnormal clones from seven patients had structural abnormalities involving either chromosomes #1 or #2, and the eighth patient had an abnormal clone that was trisomic for chromosome #1. We did not observe structural rearrangements in chromosome #14 at bands q11 or q12 in any of our cases, in contrast to previous suggestions that this chromosomal region may play a critical role in the development of T-cell lymphomas. Our findings suggest that other nonrandom chromosome abnormalities are common and may be important in the development of noncutaneous peripheral T-cell lymphomas.

Adult↗
PubMed1986

Decision analysis of the HTLV-III screening test for blood donors.

Recent research has identified the human T-lymphotropic virus type III (HTLV-III) as a probable etiologic agent of the acquired immune deficiency syndrome (AIDS). This has prompted the U.S. Public Health Service to recommend that all blood used for transfusions or in the manufacture of blood products be screened. An enzyme-linked immunosorbent assay (ELISA) has been approved for use as a screening test. From the perspective of the low-risk blood donor, however, our analysis indicates that the expected utility of no-testing may exceed that of testing. This is primarily due to the risk of a false-positive test result. It follows that informed low-risk individuals may be hesitant to donate blood. We support the discarding of blood that tests positive on ELISA but, to decrease donor risk, a positive confirmatory test, such as the Western blot, should be considered as necessary before the testing outcome is treated as positive from the donor's perspective. Additionally, individuals should be given the option to donate blood without being told the testing outcome.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Serological differences between human T-lymphotropic virus type-I (HTLV-I) and HTLV-III/LAV.

Sera from each of five preselected groups of patients with acquired immune deficiency syndrome (AIDS), AIDS-related complex (ARC), hemophilia, adult T-cell leukemia (ATL), and healthy controls were examined for antibodies to human T-cell leukemia (T-lymphotropic) virus type-I (HTLV-I) and HTLV-III by indirect immunofluorescence (IF) and radioimmunoprecipitation (RIP) methods. All sera from five patients with AIDS, ARC, and hemophilia reacted at titers from 1 : 512 to 1 : 5,120 with fixed H9/HTLV-III cells by IF but not with fixed MT-1 cells carrying HTLV-I. Similarly, sera from patients with AIDS, ARC, and hemophilia precipitated HTLV-III-specific polypeptides of 120K, 46K, and 24K. In contrast, sera from five patients with ATL did not react with fixed H9/HTLV-III cells, but reacted with fixed MT-1 cells. Moreover, HTLV-I-specific polypeptides of 68K, 28K, and 24K were precipitated with sera from ATL-patients but not with anti-HTLV-III-positive sera. Recently, we infected HTLV-I-carrying MT-4 cells with HTLV-III and provoked strong cytopathic effects. This system enabled testing for neutralizing antibodies to HTLV-III. Neutralizing titers to HTLV-III of five anti-HTLV-III-positive sera ranged from 1 : 720 to 1 : 9,000. In contrast, all five seronegative controls showed no or only low reactivity to HTLV-III envelope (1 : 80 and 100). However, three out of five anti-HTLV-I-positive sera exhibited weak cross-reactivities with HTLV-III. The reactivities were expressed as less than 1 : 160, except for one case (1 : 720). They were considered to be nonspecific since they were negative for HTLV-III antibodies in the radioimmunoprecipitation studies.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Non-Hodgkin's lymphoma after treatment of Hodgkin's disease: association with Epstein-Barr virus.

Non-Hodgkin's lymphoma occurs infrequently as a late complication of obscure cause after treatment of Hodgkin's disease. We investigated the possible role of Epstein-Barr virus in the pathogenesis of such secondary malignancies of B-cell lineage. Two patients, aged 25 and 43 years, developed high-grade non-Hodgkin's lymphomas 12 and 8 years after radiation therapy for Hodgkin's disease. Serologic profiles in these patients showed evidence of acute and past Epstein-Barr virus infections, respectively. Molecular hybridization analysis showed the presence of multiple cellular equivalents of virus genome in tumor specimens from each patient. Our findings suggest that Epstein-Barr virus may play an integral role in the pathogenesis of non-Hodgkin's lymphoma of B-cell lineage that develops after treatment of Hodgkin's disease.

Adolescent↗
PubMed1986

Prevention and treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases in immune deficient patients.

Prevention of EBV-associated lymphoproliferative diseases in immune deficient individuals is preferred; however, standard therapy for the B cell lymphomas has been successful. Chemotherapy must be given cautiously lest further immune compromise result in opportunistic infections. Recently, Acyclovir has decreased morbidity of patients with acute infectious mononucleosis in immune competent persons. In contrast, immunodeficient patients with X-linked lymphoproliferative (XLP) syndrome do not seem to respond favorably. Hence, a prospective study is underway using prophylactic immunoglobulin containing (EBV)-specific antibodies. The mortality rate is 85% following EBV infection in XLP due to fatal infectious mononucleosis associated with fulminant hepatitis and virus-associated hemophagocytic syndrome, acquired hypogammaglobulinemia or malignant B cell lymphoma. We can detect XLP by noting failure of switching from IgM to IgG antibody production on secondary challenge with bacteriophage phi X174. Also, linkage studies with the XLP locus using restriction fragment length polymorphisms are being done to detect affected males pre-EBV infection. Our rationale for prevention of phenotypes of XLP is based on observations that infants in tropical Africa and males with XLP do not develop EBV-induced diseases while neutralizing maternal antibodies are present. An EBV vaccine will be used, when available, in seronegative males with XLP. Prevention of acquired immune deficiency by screening blood for human immune deficiency virus, encouraging prudent life styles, development of specific immunosuppressive agents, development of new antiviral agents (i.e., DHPG), and identification of high risk seronegative patients offer possibilities for preventing life-threatening EBV-induced diseases.

Acyclovir↗
PubMed1986

Lymphotropic viruses, Epstein-Barr virus (EBV) and human T-cell lymphotropic virus-I (HTLV-I)/adult T-cell leukemia virus (ATLV), and HTLV-III/human immune deficiency virus (HIV) as etiological agents of malignant lymphoma and immune deficiency.

The ubiquitous, DNA herpesvirus, EBV, has B cell tropism and the geographically restricted RNA retrovirus, ATLV/HTLV-I has T cell tropism. Clinical descriptions by Burkitt and Takatsuki led to discovery of these viruses which infect silently early in life; however, ATLV is also transmitted to a spouse or by blood transfusion. In normal seropositive persons both viruses infect only 1 in about 10,000 B or T cells, respectively. EBV is associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and infectious mononucleosis. ATLV is associated with adult T cell leukemia/lymphoma and smoldering T cell lymphoma. EBV infects polyclonally and is controlled by multiple cellular and humoral control mechanisms. Escape from immune surveillance as in immune deficient African children with malaria, males with x-linked lymphoproliferative syndrome, organ transplant recipients, and AIDS patients permits conversion from polyclonal to oligoclonal and finally, monoclonal malignancy. T cell immune defects permit proliferation of cells which undergo molecular and/or cytogenetic alterations. In contrast to EBV, which is integrated and nonintegrated in B cells, ATLV is monoclonally integrated. Viral transforming proteins and immune suppressive substances are produced. Immune deficiency in silent carriers of ATLV and in those with smoldering ATL suggest that immune surveillance deters emergence of ATL. Prevention of primary infection by vaccination against these lymphotropic viruses, and use of immunotherapy and antiviral drugs may potentially retard conversion of infected B or T cells to monoclonal malignancy.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Acquired immune deficiency syndrome (AIDS).

The epidemiology, clinical and pathologic manifestations, identification of groups at high risk, results of laboratory analyses, and description of the modes of transmission of the putative etiologic agent HTLV-III/LAV have been summarized. Mechanisms of induction of T-cellular immunodeficiency have been described, including the role of HTLV-III/LAV, and possible roles of CMV and EBV as cofactors have been presented. Prospects for preventing and treating AIDS have been succinctly summarized.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Epstein-Barr virus (EBV) and X-linked lymphoproliferative syndrome (XLP).

XLP was first described in 1975, when EBV was still focused on as an immediate oncogenic agent, but with some uncertainties raised by the absence of EBV in most non-endemic Burkitt lymphoma. The discovery of XLP refreshingly evidenced and popularized the concept, "EBV pathogenicity (oncogenicity) in immunocompromised hosts", which was later vastly substantiated by EBV-carrying lymphomas in organ-transplanted and AIDS patients. Fatal (or severe) IM, acquired hypogammaglobulinemia (AH) and malignant lymphoma (MH) are 3 major phenotypes in XLP. Fatal IM occurs in 2/3 with a mortality rate of 85%. Lymphocyte infiltration (T cells and EBV-positive B cells) followed by their depletion with the appearance of macrophages. EBV-associated hemophagocytic syndrome in the bone marrow leads to hematocytopenia, ML, AH and ML with AH usually occur after EBV infection, but can occur before it. Reactivation pattern of EBV serology (high VCA, high EA, low EBNA), impaired generation of EBV-specific killer cell (poor regression), lowered NK activity, lowered 4/8 ratio and failure to mount IgG response to phi X174 have been recorded in XLP and carrier females. However, some or all of these are also found in non-XLP congenital immunodeficiencies as well as acquired immunodeficient states like advanced lymphoma or AIDS. In order to record XLP-specific defects, impaired help of autologous Ia-stimulated T4 cells or exaggerated suppression by T cells exposed to MA-pulsed macrophages is now being tested (Purtilo, personal communication). Fewer V region genes of T receptor may be a possibility. Restriction fragment length polymorphism (RFLP) by using probes from X chromosome may substantiate the precise genetics of this disease.

Agammaglobulinemia↗
PubMed1985

Host cell range of adult T-cell leukemia virus. I. Viral infectivity and binding to various cells as detected by flow cytometry.

Adult T-cell leukemia virus is the member of a human type-C retrovirus family (HTLV) found to be associated with adult T-cell leukemia (ATL) in Japan. In our study, HTLV was isolated from the MT-2 cell line, purified on sucrose gradient and labelled with fluorescein-isothiocyanate (FITC-HTLV). The protein pattern of the virus was determined by SDS-gel electrophoresis and assured by Western blotting using ATL patient serum. Fresh human lymphocytes, separated B and T cells, mouse and rabbit lymphocytes, mouse fibroblasts, and 13 different tumor cell lines were tested in parallel for binding of FITC-HTLV and infectability by the virus. Virus binding to cell receptors was assayed by flow cytometry. Successful infection was monitored by following the expression of HTLV-determined antigen (HTLA). Most of the cells bound FITC-HTLV at levels ranging from 5% to 130% of the MT-2 cell binding. Only fresh human T, mouse and rabbit lymphocytes were infectable by cell-free virus preparations. The results demonstrate that HTLV receptors are present on different types of cells of both human and animal origin, and that infection by the virus is restricted to fewer host cells but not limited to a specific class of human lymphocytes.

Animals↗