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Biomedical subjects

J L Sullivan

Publications and source records attributed to J L Sullivan.

At least 199 records · Page 11Linked to original sources
PubMed1986

Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses.

The relationship between hemophiliac immunodeficiency and exposures to factor VIII concentrate, LAV/HTLV-III retrovirus, and infection with Epstein-Barr virus and cytomegalovirus was examined. Exposure to factor VIII concentrate was significantly correlated with decreased percentages of T helper/inducer cells, decreased T helper/suppressor cell ratios, and decreased proliferative responses to plant mitogens. LAV/HTLV-III seropositivity was the primary predictor of increased percentages of HLA-DR-bearing mononuclear cells and decreased proliferative responses to pokeweed mitogen. Epstein-Barr virus and cytomegalovirus infections acted in a synergistic manner with LAV/HTLV-III to produce immunoregulatory defects. Increased percentages of T suppressor cells and decreased delayed cutaneous hypersensitivity skin test responses were observed in LAV/HTLV-III seropositive hemophiliacs infected with Epstein-Barr or cytomegalovirus. We conclude that hemophiliacs receiving commercial factor VIII concentrate experience several stepwise incremental insults to the immune system: alloantigens in factor VIII concentrate, LAV/HTLV-III infections, and herpesvirus infections.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Serological characterization of HTLV-III infection in AIDS and related disorders.

Current efforts to test blood donors and other persons for exposure to the human T cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), are based on the measurement of serum antibodies to viral antigens. We studied presence of serum antibodies to HTLV-III-related antigens from 767 individuals with AIDS or AIDS-related complex (ARC) or asymptomatic persons at risk for AIDS by using ELISA and immunoblot techniques. Of the 280 specimens from AIDS and ARC subjects that were tested, 99% were ELISA reactive and 96% were immunoblot reactive. Greater than 96% of the seropositive subjects manifested antibodies to the p24 core antigen, whereas only 88% had antibodies to the gp41 envelope-related glycoprotein. Contrary to previous reports, a short incubation time in the immunoblot assay failed to detect low-titer or low-affinity antibodies that were detected by overnight incubation. There was no apparent difference in pattern of antibodies to HTLV-III-related antigens in symptomatic vs. asymptomatic seropositive individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Pathogenesis of B cell lymphoma in a patient with AIDS.

Lymphoma occurs at increased frequency in patients with the acquired immunodeficiency syndrome (AIDS). We studied, using serologic and molecular techniques, one such lymphoma for (a) evidence of infection with human T lymphotropic virus, type III (HTLV-III), and Epstein-Barr virus (EBV), (b) monoclonal rearrangement of immunoglobulin and T cell receptor genes, and (c) rearrangement of the c-myc oncogene. Immunoglobulin and T cell receptor gene studies demonstrated that the tumor was of monoclonal B cell origin. Similar to cases of Burkitt's lymphoma unrelated to AIDS, there were DNA sequences in the lymphoma that hybridized to EBV-specific probes and demonstrated evidence of c-myc rearrangement. HTLV-III sequences were not detected in the malignant B cells. The pathogenesis of some B cell neoplasms in patients with the syndrome may involve transformation by EBV and deregulation of oncogene expression without direct infection of the malignant B cells by HTLV-III.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The in vitro growth, heterotransplantation, and differentiation of a human rhabdomyosarcoma cell line.

A human rhabdomyosarcoma (RMS) cell line was established from a case of childhood small cell sarcoma, which in vivo showed no evidence of differentiation, but which demonstrated myogenic differentiation in tissue culture. In a serum-free culture medium, the tumor cells demonstrated continuous growth without ultrastructural or biochemical evidence of differentiation. Heterotransplanted RMS cells gave rise to tumors in nude mice which also showed no myogenic differentiation. However, RMS cells grown in the presence of either retinoic acid (5 microns), phorbol ester (1 nM), prostaglandin E1 (10 ng/ml), or 2% fetal calf serum gave rise to myotubes with a biochemical shift in the creatine kinase isoenzyme pattern from the embryonic to the mature skeletal muscle form. The karyotype of the RMS cells revealed a translocation of Chromosomes 2 and 13, which may represent a nonrandom aberration unique to this morphologic subtype. In addition, the RMS cells gave evidence for gene amplification in the form of double minute chromosomes. This human RMS cell line provides a valuable in vitro system for study of myogenesis and factors which induce differentiation.

Cell Differentiation↗
PubMed1985

Chronic T-cell lymphocytosis with neutropenia. Its association with Epstein-Barr virus infection.

Chronic T-cell lymphocytosis with neutropenia has primarily been reported in adults. We have cared for a 14-year-old patient with this condition for over five years. This patient consistently had greater than 90% lymphocytes in his differential cell count. The majority of these cells had the OKT8 phenotype. Serologic studies demonstrated evidence for a chronic Epstein-Barr infection with elevated antibody titers to both early antigen and to the viral capsid antigen. Patients presenting with this condition should be carefully evaluated for possible viral infection.

Adolescent↗
PubMed1985

Lymphoma of host origin in a marrow transplant recipient in remission of acute myeloid leukemia and receiving cyclosporin A.

Lymphomas are an uncommon complication of solid organ transplantation and rarely occur after marrow transplantation. When post-marrow transplant lymphomas have occurred, they have been of donor cell origin and when sought, Epstein-Barr virus DNA has been found in the tumor. A 21-year-old woman developed a poorly differentiated lymphocytic lymphoma 6 months after bone marrow transplantation for acute myeloid leukemia in remission. Cyclosporin A had been used as an immunosuppressant. A chromosomal polymorphism demonstrated that the tumor was of host origin and contained a monoclonal tumor marker, 46,XX INV 4 (p16q12). The tumor did not contain the DNA of the Epstein-Barr virus.

ABO Blood-Group System↗
PubMed1985

Immunoregulation during acute infection with Epstein-Barr virus: dynamics of interferon and 2',5'-oligoadenylate synthetase activity.

Immunoregulation during acute infection with Epstein-Barr virus (EBV) is incompletely understood, although species of interferon (IFN) may be important immunoregulatory molecules. IFN, 2',5'-oligoadenylate (2',5'-A) synthetase (an IFN-induced enzyme), T and natural killer cell subsets, and natural and anomalous killer cell functions were studied systemically during acute infectious mononucleosis. Serum IFN was not detected (less than 1 international unit/ml) during infection. 2',5'-A synthetase activity was significantly increased in the acute phase of infection when compared with convalescence (34.5 +/- 6.5 vs. 3.6 +/- 1.2 nmol ATP/mg of protein per hr; P less than .01 by Student's t test). A generalized IFN effect was suggested by elevated 2',5'-A synthetase activity in purified neutrophil preparations. Sequential studies revealed a correlation between peak elevations of 2',5'-A synthetase activity and increased percentages of cytotoxic/suppressor cells as well as anomalous killer cell activity against an EBV-infected B cell line. Thus IFN may act as an immunoregulatory lymphokine early in the course of acute EBV infection.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Herpesvirus sylvilagus infects both B and T lymphocytes in vivo.

Herpesvirus sylvilagus infection of cottontail rabbits (Sylvilagus floridanus) was studied as a model of herpesvirus-induced lymphoproliferative disorders. Leukocytosis, splenomegaly, proliferation of T cells and virus production by lymphocytes characterized this infectious mononucleosis-like disease. Approximately two copies of circular herpesvirus sylvilagus genomes per cell were detected in spleen cells at 2 weeks postinfection, and circular genomes could still be observed after 4 months. Circular viral genomes were found in both B and T lymphocytes. Small amounts of linear viral DNA (0.1 to 0.3 copies per cell) were also detected in both B and T cells. These results indicated that the virus did not replicate in the majority of lymphocytes in vivo. Herpesvirus sylvilagus infection in cottontail rabbits could be useful as a model for studying the complex virus-host relationships of lymphotropic herpesviruses and perhaps as an animal model for Epstein-Barr virus infection in humans.

Animals↗
PubMed1985

Epstein-Barr virus infections in hairy cell leukemia patients in the presence of complement-dependent neutralizing antibody.

Immune system status was characterized in patients with hairy cell leukemia (HCL) with respect to explaining their chronic or recurrent infections with Epstein-Barr virus. Measures of cellular immune responsiveness for a group of 11 HCL patients were, in general, decreased when expressed as the proportion of tested patients with values less than 2 S.D. below mean values for a group of 17 healthy adults: T-cell enumeration, seven of 13; mitogen responsiveness of phytohemagglutinin, 10 of 11; concanavalin A, 10 of 11; pokeweed mitogen, 10 of 11; B-cell responsiveness by anti-immunoglobulin immunobead stimulation, two of six; responsiveness to streptolysin O antigen, four of seven; mixed-lymphocyte reaction, six of seven; natural killer cell activity, six of eight. Specific immunity to Epstein-Barr virus was measured by complement-independent, antibody-mediated virus neutralization (mean index for HCL patients being 56% of control value) and complement-dependent virus neutralization (98% of control value). We concluded that, in spite of depressed levels of immune responses measured with general, cellular assays, functional levels of complement-dependent virus-neutralizing antibody were present in these HCL patients.

Antibodies, Viral↗
PubMed1985

Epstein-Barr virus-associated hemophagocytic syndrome: virological and immunopathological studies.

The virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by a benign, generalized histiocytic proliferation, with marked hemophagocytosis associated with systemic viral infections. We have studied the virological and immunopathological events occurring in two children experiencing Epstein-Barr VAHS. Neither of the patients had an underlying immunodeficiency and both recovered from their disease and are completely well one year after follow-up. In each patient, evidence for primary Epstein-Barr virus (EBV) infection was documented with a typical humoral immune response, including IgM antibody directed against virus capsid antigen. EBV was demonstrated in lymphoreticular tissues by electron microscopy and molecular hybridization studies. Permissive EBV infection was suggested by the finding of mature virus particles and linear viral DNA in lymphoreticular tissues. Immunopathological studies demonstrated complete effacement of lymph node architecture by a marked proliferation of immunoblasts in patient 1 and infiltration and effacement of the lymph node architecture with benign-appearing histiocytes in patient 2. Atypical lymphocytes characteristic of acute EBV infection were notably absent in the peripheral blood of both patients and cytotoxic T cells, which normally lyse EBV-infected B cells, were also absent from the peripheral circulation. Our observations suggest that EBV-induced VAHS may be the result of an increased virus burden in the face of immunoregulatory cell imbalances.

Bone Marrow Examination↗
PubMed1984

Analysis of cytomegalovirus and Epstein-Barr virus antibody responses in treated hemophiliacs. Implications for the study of acquired immune deficiency syndrome.

One hundred hemophiliacs were studied for serological evidence of infection with cytomegalovirus (CMV), Epstein-Barr virus (EBV), and hepatitis B virus. Ninety-eight percent had markers of hepatitis B infection, while 69% had antibody to EBV and only 42% had antibody to CMV, suggesting that factor VIII preparations do not transmit EBV and CMV efficiently. Seventy-one percent of those seropositive to EBV had an antibody pattern suggestive of active infection, as compared with 23% of healthy young adult blood donors. These findings make the patients with hemophilia an unusually favorable population for the study of the role of persistent viral infection in the immunodeficiency now found to be widespread in groups at high risk for acquired immune deficiency syndrome (AIDS) and for the contribution of CMV and EBV to AIDS itself.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Neutral amino acid transport and in vitro aging.

Human fibroblasts possess five distinguishable systems for amino acid transport. Initial rates for three of these decline with in vitro age. The decline most noticeably affects the L system, whose rate for L-phenylalanine transport at 10 microM declines by 44% between the 27th and 39th population doubling levels. Accumulation of L-phenylalanine is similarly affected. The insensitivity of older cells to reduction of the amino acid concentration in culture medium casts doubt on possible interpretation of the transport decline as a causal factor in limiting growth.

Alanine↗
PubMed1984

Acute psychosis in a 45-year-old man with bipolar disorder and primary Epstein-Barr virus infection: a case report.

A 45-year-old physician with bipolar disorder presented with an acute organic psychosis, fever, and hematologic and serologic findings of a primary Epstein-Barr virus infection. Pathogenesis was complicated by the history of discontinued lithium therapy prior to the psychosis. The patient recovered completely. Literature concerning psychosis and infectious mononucleosis is reviewed.

Acute Disease↗
PubMed1984

Complement-dependent, Epstein-Barr virus-neutralizing antibody appearing early in the sera of patients with infectious mononucleosis.

The first serum specimens obtained after onset of illness and those obtained later from patients with infectious mononucleosis were examined for neutralization of P3HR-1-derived Epstein-Barr virus (EBV). Without complement, viral neutralization indices of sera obtained soon after onset were all less than 0.2, and those of sera obtained later were less than 0.5. In contrast, sera from EBV-seropositive, healthy adults had neutralization indices of 0.45-1.0. Sera from EBV-seronegative adults showed no evidence of viral neutralization. The addition of complement from EBV antibody-negative human serum to 31 early and 34 late serum samples from 34 patients with infectious mononucleosis yielded neutralization indices of greater than or equal to 0.95. Complement-dependent neutralizing antibodies were also demonstrated in sera from EBV-seropositive, healthy adults. In contrast, sera from EBV-seronegative adults failed to neutralize EBV after the addition of complement. Heat inactivation destroyed the capacity of complement to induce additional neutralization of EBV by sera from patients with mononucleosis. The early appearance of complement-dependent neutralizing antibodies in the course of mononucleosis is consistent with a role in recovery from acute EBV infection.

Antibodies, Viral↗