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Biomedical subjects

D T Purtilo

Publications and source records attributed to D T Purtilo.

At least 163 records · Page 9Linked to original sources
PubMed1981

Cellular immune defects to Epstein-Barr virus-determined antigens in young males.

Three males with the X-linked lymphoproliferative syndrome (XLP) with hypo- or agammaglobulinemia following Epstein-Barr virus (EBV) infection and two males with the chronic mononucleosis syndrome were investigated for immune responses to EBV-determined antigens. Males with XLP showed profound cellular immune defects. Markedly diminished responses of natural killer cell and interferon-activated killer cell activities and impaired leukocyte migration inhibition responses to phytohemagglutinin were determined in patients with XLP. The two patients with chronic mononucleosis showed less severe defects. All patients showed partial or complete impairment of their EBV-specific immune responses as measured by leukocyte migration inhibition. EBV-specific antibodies were markedly diminished against EBV-associated nuclear antigen, early antigen, and viral capsid antigen in males with XLP. In contrast, patients with chronic mononucleosis had elevated antibodies to most EBV-specific antigens. Individuals with life-threatening EBV-induced lymphoproliferative disorders may exhibit multiple defective immune mechanisms against the virus.

Adolescent↗
PubMed1981

The Epstein-Barr virus in the pathogenesis of posttransplant lymphoproliferative disorders. Clinical, pathologic, and virologic correlation.

Twelve renal transplant patients with lymphoproliferative disorders (LPDs) were studied. Two clinical patterns were identified: (1) Young patients present with an infectious mononucleosis-like illness with fever, sore throat, and lymphadenopathy soon after transplantation or antirejection therapy. Many organs are ultimately involved, and the clinical course is one of a rapidly fatal LPD. (2) Older patients present a longer time after transplantation with symptoms of solid tumors involving the central nervous system, oropharynx, liver, or small bowel. The clinical course is slower, but it is progressive and fatal. Morphologically these LPDs can all be classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic diffuse B-cell lymphoma (PBL). Cell marker studies in four patients demonstrated a polyclonal B-cell proliferation. Transition from a polyclonal B-cell proliferation to a monoclonal tumor may occur. Epstein-Barr virus (EBV) specific antibody titers, anticomplement immunofluorescence staining of tumors for the presence of the Epstein-Barr nuclear antigen (EBNA), and EBV complementary ribonucleic acid (cRNA)/deoxyribonucleic acid (DNA) hybridization and vDNA/DNA reassociation analysis implicate EBV as the probable etiologic agent in these disorders. Successful management of these lethal LPDs may depend on discontinuation of immunosuppression and removal of the allograft. Antiviral therapy, however, may prove to be useful.

Adolescent↗
PubMed1981

Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative diseases by clinical, virological, and immunopathological studies.

Multiple methods, pedigree analysis, clinical evaluation, and Epstein-Barr virus (EBV)-specific serology, EBV DNA hybridization of tissues to probe for viral genome, staining of touch imprints for EBV nuclear-associated antigen, establishment of spontaneous infected B-cell lines from peripheral blood or tissues, examination of peripheral blood smears, and hematopathology studies, were used to study seven patients with the X-linked lymphoproliferative syndrome and seven additional patients with life-threatening EBV-associated diseases. These studies demonstrated EBV in the tissues of all 14 patients and immunodeficient antibody responses to EBV were documented. This virus can produce various life-threatening lymphoproliferative diseases in a variety of immunodeficient patients.

Adolescent↗
PubMed1981

Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative diseases by Epstein-Barr virus complementary RNA/DNA and viral DNA/DNA hybridization.

Tissues from patients thought to have Epstein-Barr virus (EBV)-induced lymphoproliferative diseases were probed for EBV genomes using 2 independent hybridization techniques. Tissues from six patients with the X-linked lymphoproliferative syndrome, all five renal allograft recipients with immunoblastic sarcoma, and eight patients with diverse types of immunodeficiency and lymphoproliferative diseases such as fatal infectious mononucleosis or malignant lymphoma associated with antecedent immunodeficiency contained significant numbers of EBV genome equivalents per cell. The use of 2 hybridization probes is recommended to confirm the presence of EBV genomes. The finding of significant numbers of EBV genomes in tissues from patients with immunodeficiency suggests that EBV is the etiological agent of the associated lymphoproliferative diseases.

Adolescent↗
PubMed1981

Diverse familial malignant tumors and Epstein-Barr virus.

Continued monitoring of a family for new malignant tumors has revealed diverse immunological and neoplastic disorders during a 15-year period. In 1966, the proband developed lymphoma. In 1975, his antibody titers to Epstein-Barr virus (EBV) became elevated, and again, he developed a malignant lymphoma. He also had borderline hypo-immunoglobulin A, died of glioblastoma multiforme in 1977, and at autopsy, had adenomatous colonic polyps. His eldest brother has normal immunoglobulin levels, but developed immune thrombocytopenia in 1973 and had elevated EBV antibody titers in 1980. Another brother had hypo-immunoglobulin A, thymoma in 1965, and adenomas and adenocarcinoma of the colon. Two other brothers succumbed to glioblastoma in 1968 and 1969. The father of the proband had bronchiectasis in 1952, hypo-immunoglobulin M documented in 1972, and elevated EBV antibody titers 5 years preceding development of a malignant lymphoma. The latter contained 10 EBV genome equivalents/cell by EBV viral DNA/DNA reassociation kinetics analysis. The proband's grandmother had died of an immunoglobulin G-secreting myeloma in 1977, and his grandfather had borderline low immunoglobulin M, elevated EBV antibody titers, and hypopharyngeal carcinoma in 1980. Predisposition to oncogenesis in this family was probably inherited.

Adenocarcinoma↗
PubMed1981

Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus.

Six renal transplant recipients with abnormal lymphoproliferative disorders were studied in an attempt to define their clinical features and the role of Epstein-Barr virus (EBV) in their pathogenesis. Patients were either teenage (three) or in the sixth decade (three). The younger patients presented an average of 3 months after transplantation with fever, sore throat, and lymphadenopathy; had been markedly immunosuppressed; frequently had preceding or concomitant cytomegalovirus infections; and two of three had a rapidly fatal course. The older patients presented an average of 5 years after transplantation while on maintenance immunosuppressive drugs; in two of three cases with an oropharyngeal tumor; and had a more indolent, but frequently fatal, clinical course. The most frequent sites of biopsy-proven involvement in these patients were lymph nodes (three), the oropharynx (three), liver (three), bone marrow (three), transplanted kidney (three), colon (two), and central nervous system (two). EBV-specific antibody titers including anti-viral capsid antigen IgG, anti-viral capsid antigen IgM, anti-early antigen, and anti-Epstein-Barr nuclear antigen were serially measured in all patients. Four patients demonstrated serological evidence of a primary (one) or reactivation (three) EBV infection. No patient had significant changes in anti-early antigen or anti-Epstein-Barr nuclear antigen titers. All three patients tested for oropharyngeal shedding of EBV were positive. A touch imprint of one tumor was stained for the presence of Epstein-Barr nuclear antigen, and a majority of cells were positive. EBV complementary RNA/DNA filter hybridization and/or viral DNA/DNA reassociation analysis performed on tumor biopsy specimens in five patients demonstrated multiple EBV genome equivalents per cell in all eight specimens tested. Clinical, pathological, serological, and molecular hybridization studies provide substantial evidence that EBV was the cause of these lymphoproliferative disorders occurring after renal transplantation. Impaired host defenses allow the EBV-transformed B-lymphocytes to escape normal control mechanisms. This impairment is invariable and influenced by many factors resulting in the observed spectrum of disease. Cytogenetic changes, however, may also be important.

Adolescent↗
PubMed1981

X-linked lymphoproliferative syndrome. An immunodeficiency disorder with acquired agammaglobulinemia, fatal infectious mononucleosis, or malignant lymphoma.

The X-linked lymphoproliferative syndrome (XLP) is characterized by a combined variable immunodeficiency with vulnerability to Epstein-Barr virus (EBV)-induced fatal or chronic infectious mononucleosis, acquired agammaglobulinemia, aplastic anemia, or malignant B cell lymphomas. Diagnosis of XLP requires documentation of two or more maternally related males with these phenotypes. Epstein-Barr virus must be demonstrated in circulating blood, lymphoid tissues, or saliva of infected males. Characteristically, the patients have low-titer antibodies to EBV and often lack anti-EB nuclear-associated antibody due to T cell defects. Thymus gland is often depleted and epithelium may be destroyed. Thymic-dependent regions in lymph nodes and spleen are depleted and immunoblastic transformation with plasma cell differentiation is seen. The carrier females exhibit partial immune deficiency and have paradoxically elevated antibodies to EBV. Our registry of XLP provides consultation and comprehensive study of persons and families with the syndrome.

Agammaglobulinemia↗
PubMed1980

Deficient natural killer cell activity in x-linked lymphoproliferative syndrome.

The activity of natural killer cells was found to be deficient in 10 of 12 males with X-linked lymphoproliferative syndrome, a life-threatening proliferation of lymphocytes after infection by Epstein-Barr virus. The activity levels of natural killer cells from affected males were increased after treatment with interferon in vitro, but normal levels of killing were not obtained. Deficient activity of killer cells in individuals with immunodeficiency and chronic infection by Epstein-Barr virus may contribute to the development of lymphoproliferative disorders.

Adolescent↗
PubMed1980

Epstein-Barr-virus-induced oncogenesis in immune-deficient individuals.

Experimental and clinical evidence supports the notion that the Epstein-Barr virus (EBV) can become oncogenic in immune-deficient hosts. Renal transplant recipients and children with inherited immune deficiency are at high risk for lymphomagenesis. Defective immune responses to EBV permit persistence of polyclonal proliferation of B cells. Conversion from polyclonal to monoclonal proliferation is probably the result of a cytogenetic error in a B cell. This hypothesis can be tested prospectively in patients with immune deficiency by immunological, EBV, and genetic studies.

Animals↗
PubMed1980

Persistent transfusion-associated infectious mononucleosis with transient acquired immunodeficiency.

Trauma and blood transfusion led to profound, persistent infectious mononucleosis in a 21 year old man. Splenectomy and trauma had apparently produced transient immune deficiency which was complicated by osteomyelitis of a fractured tibia. The transfused blood probably contained Epstein-Barr virus (EBV). Infectious mononucleosis had ensued 25 days after a blood transfusion was given, antibodies to EBV appeared in his serum, and the infectious mononucleosis persisted for nearly two years. His immunity returned gradually to normal, but because of nonunion of the fracture site, which was infected by Staphylococcus aureus, above-knee amputation was required. The acquired, transient immune deficiency to EBV and profound infectious mononucleosis seen in this patient is analogous to inherited, permanent immune deficiency to this virus in the X-linked lymphoproliferative syndrome.

Adult↗
PubMed1980

X-linked lymphoproliferative syndrome registry report.

Immune deficiency, especially to the Epstein-Barr virus, and increased susceptibility to fatal infectious mononucleosis, acquired agammoglobulinemia, and lymphoma are the cardinal features of the X-linked lymphoproliferative syndrome. Since the establishment of the XLP Registry in September, 1978, 59 affected males in seven unrelated kindreds were comprehensively studied. A spectrum of lymphoproliferative phenotypes was observed. Thirty-four patients (57%) died from infectious mononucleosis, eight (14%) had fatal infectious mononucleosis with lymphoma (immunoblastic sarcoma), nine (15%) had depressed immunity following EBV infection, and eight (14%) developed lymphoma. Several patients with XLP lacked EBV antibodies despite infection by EBV. The results of this study suggest that EBV can be an oncogenic agent in patients who are immune deficient with XLP.

Adolescent↗