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Biomedical subjects

J L Sullivan

Publications and source records attributed to J L Sullivan.

At least 217 records · Page 12Linked to original sources

Circular Herpesvirus sylvilagus DNA in spleen cells of experimentally infected cottontail rabbits.

Cottontail rabbits (Sylvilagus floridanus) were infected with Herpesvirus sylvilagus, and spleen cells were analyzed for the presence of virus-specific, covalently closed circular, and linear DNA molecules by a simple electrophoretic technique, followed by transfer to nitrocellulose filters and hybridization with cloned viral DNA (Gardella et al., J. Virol. 50:248-254, 1984). Approximately 0.2 copies per cell of circular DNA and 0.2 copies per cell of linear DNA were detected by hybridization with a cloned viral DNA fragment. The size of the viral DNA was estimated at ca. 158 kilobase pairs. Restriction endonuclease patterns suggested structural similarities to cottontail herpesvirus DNA.

Animals↗

Atypical depression.

Atypical depressions are those characterized by high levels of phobic anxiety or by reversed vegetative symptoms such as hypersomnia and hyperphagia. Patients with such depressions may present overtly for treatment. However, they may also present within other diagnostic categories such as personality disorder or somatic complaints. The comparative roles of monoamine oxidase inhibitors, heterocyclic antidepressants, and other biologic treatments for atypical depressions are discussed.

Alprazolam↗

Analysis of transformation with Epstein-Barr virus and phenotypic characteristics of lymphoblastoid cell lines established from patients with hairy cell leukemia.

In order to assess the role of Epstein-Barr virus (EBV) in patients with hairy cell leukemia (HCL), we have sought to characterize 1) the ability of EBV to infect and transform hairy leukemic cells in vitro and 2) the phenotypes of cell lines putatively derived from those leukemic cells. Analysis of EBV-induced transformation and the kinetics of Epstein-Barr nuclear antigen (EBNA) induction in leukemic preparations indicated that most leukemic cells were not susceptible to EBV infection but that at least a small subpopulation of leukemic cells could be infected with EBV. Lymphoblastoid cells lines were established after exposure of peripheral blood or splenic cells from HCL patients to B95-8 or QIMR-WIL EBV. Splenic leukemic cell preparations were more sensitive targets for EBV transformation than were peripheral blood cell samples. The newly established cell lines, but not long-established B lines such as Raji, demonstrated high levels of synthesis of p35, (a protein complex expressed abundantly by cells of a subset of HCL patients) and high levels of tartrate-resistant acid phosphatase (an enzyme relatively diagnostic for HCL). Lymphoblastoid lines from one patient with HCL expressed lambda light chains and no kappa chains as did the patient's leukemic cells. Virus expression in these lines showed that HCL-derived lines had spontaneous early antigen (EA) and viral capsid antigen (VCA) expression. Transforming EBV could be rescued from HCL-derived cell lines but not from cord blood-derived lines.

Acid Phosphatase↗

Epstein-Barr virus-infected B lymphoblastoid cell lines: dynamics of interferon and 2'5'-oligoadenylate synthetase activity.

Levels of 2'-5'-oligoadenylate synthetase (2'-5'OAS) activity measured in cell-free extracts of 23 Epstein-Barr virus transformed beta lymphoblastoid cell lines (LCL) were measured. Enzyme activity was low during stationary or log phase growth, and rapidly rose to peak values during log phase. Peak levels of 2'-5'OAS activity were characteristic for each LCL, and were significantly higher (P less than 0.05) in lines derived from patients with infectious mononucleosis (IM) than in lines from healthy individuals. Peak 2'-5'OAS activity correlated with maximal titers of endogenous human interferon-alpha (HuIFN-alpha); (r = 0.80). Enzyme activity levels could be increased by treating LCLs with exogenous HuIFN-alpha, or decreased by neutralization of endogenous interferon with antibody to HuIFN-alpha. 2'-5'OAS activity always peaked during log-phase growth, even in cultures depleted of interferon by antibody and in cultures which did not produce interferon. Thus, although peak levels of 2'-5'OAS activity in a given LCL correlated with maximal interferon titers, the growth phase associated variations in enzyme activity were independent of interferon. We conclude that regulation of constitutive levels of 2'-5'OAS in LCLs is partially independent of interferon.

2',5'-Oligoadenylate Synthetase↗

X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency.

The X-linked lymphoproliferative syndrome is characterized by immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. We studied immune responses in six males of a well-characterized kindred with the X-linked lymphoproliferative syndrome. Two males were studied before and during acute fatal EBV infection. Both individuals demonstrated normal cellular and humoral immunity before EBV infection. During acute EBV infection, both individuals developed vigorous cytotoxic cellular responses against EBV-infected and -uninfected target cells. Anomalous killer and natural killer T cell activity was demonstrated against a variety of lymphoid cell lines, autologous fibroblasts and autologous hepatocytes. Effector cells responsible for anomalous killing reacted with a pan-T cell monoclonal antibody, and belonged to the OKT.8 T cell subset. Death in each case was caused by liver failure, but one patient developed extensive liver necrosis, whereas the other developed a massive infiltration of the liver with EBV-infected immunoblasts after aggressive immunosuppressive therapy. Immunological studies were performed on four males who had survived EBV infection years previously. They demonstrated global cellular immune defects with deficiencies of lymphocyte proliferative responses to mitogens and antigens, humoral immune deficiencies, abnormalities of regulatory T cell subsets and deficient natural killer cell activity. We propose that an aberrant immune response triggered by acute EBV infection results in unregulated anomalous killer and natural killer cell activity against EBV infected and uninfected cells. These studies suggest that global immune defects appearing in males with X-linked lymphoproliferative syndrome who survive EBV infection are epiphenomenon.

Adolescent↗

Persistent epstein-barr virus infection mimicking juvenile chronic myelogenous leukemia: immunologic and hematologic studies.

Epstein-Barr virus (EBV) infections may induce a diverse clinical picture, ranging from the well characterized infectious mononucleosis (IM) syndrome to the rare X-linked lymphoproliferative syndrome. We describe two unrelated children, a 21-mo-old white boy and a 15-mo-old black girl, who presented with the clinical and laboratory findings characteristically seen in juvenile chronic myelogenous leukemia (JCML). Results of periodic serodiagnostic tests indicated that they likely have persistent infection with EBV. Both had elevated IgG antibody to viral capsid antigen (greater than or equal to 1:320) and antibody to early antigen (1:20-1:40) that have persisted for 3 yr of more. Both patients had EBV-specific suppressor cell activity, decreased natural killer cell activity, and diminished antibody-dependent cell-mediated cytotoxicity (ADCC) activity. These changes suggest an underlying defect in the immunoregulatory network controlling EBV infection. The patients have shown clinical improvement without treatment. It appears that EBV infections are capable of inducing symptoms similar to those seen in JCML. Careful evaluation for evidence of EBV infection in patients presenting with symptoms compatible with JCML seems warranted.

Animals↗

Treatment of life-threatening Epstein-Barr virus infection with acyclovir.

Two pediatric patients with life-threatening Epstein-Barr virus infections were studied immunologically and treated with acyclovir [9-(2-hydroxyethoxymethyl) guanine]. The patient with chronic active Epstein-Barr virus infection who experienced massive hepatosplenomegaly, pancytopenia, and failure to thrive demonstrated abnormalities of T and B lymphocytes. A second patient, with the X-linked lymphoproliferative syndrome, experienced a rapidly fatal course of acute Epstein-Barr virus infection which typifies this yet undefined immunodeficiency to Epstein-Barr virus. In each case, objective evidence for clinical improvement or antiviral effect of acyclovir treatment was not apparent. Abnormally productive Epstein-Barr virus infections did not appear to play a major role in the clinical syndromes observed. Current studies are focused on treatment of immunologically normal patients with early complicated Epstein-Barr virus infection.

Acyclovir↗

Atypical depression.

The term atypical depression generally indicates either depression accompanied by severe anxiety (type A) or by atypical vegetative symptoms, ie, increased appetite, weight, sleep, or libido (type V). Early age at onset, predominance in women, outpatient status, mild intensity, rarity of attempted suicide, nonbipolarity, nonendogenicity, and minimal psychomotor change are common to both types. Some types of bipolar depression may be considered as atypical if accompanied by reversed vegetative change. Monoamine oxidase inhibitors are more effective than placebo in treating atypical depression, but their reported superiority to tricyclic antidepressants awaits confirmation, for which the development of appropriate operational criteria would be helpful. Atypical depression is a term that covers several types of depressive disorder and can, for the most part, be better defined using the standard nomenclature.

Adult↗

Treatment of the "on-off" phenomenon in Parkinsonism with lithium carbonate.

Six patients with severe parkinsonism complicated by the "on-off" phenomenon were treated with lithium carbonate in addition to regular antiparkinson medications. A randomized double-blind crossover trial of lithium versus placebo was conducted, followed by an open trial of lithium therapy. Five patients had markedly reductions in akinesia (mean, 70%) and improved by one grade in Parkinson staging. This result was more striking in male than in female patients, and in all responders benefit has been maintained during the open phase of lithium treatment (mean follow-up of 36 weeks). In no patient was a reduction in akinesia observed during placebo treatment. Lithium carbonate appears to offer a new and potentially effective approach to treatment of the on-off phenomenon.

Adult↗

In vitro responses to a B-lymphoblastoid cell line in immunodeficiency diseases.

The use of a B-lymphoblastoid cell line (B-L-CL) as a stimulator cell in the mixed leukocyte reaction (MLR) was investigated in patients with immunodeficiency disorders. The kinetics of the MLR stimulated by B-L-CL are similar to those stimulated by normal allogeneic leukocytes, however, B-L-CL stimulate a greater quantitative response. Comparison of a LCL-stimulated and normal allogeneic lymphocyte-stimulated MLR in 32 patients and normal controls demonstrated that variation in the MLR was reduced when B-LCL were used as stimulator cells. The decrease in variability allowed for more sensitivity in the determination of abnormal responses; 9 of 32 patients had abnormal B-LCL-stimulated MLC responses, compared with 5 of 32 patients with abnormal responses to normal allogeneic leukocytes. Dose-response studies showed that vigorous responses could be obtained with low doses of B-LCL stimulator cells which served to better define deficient patient responses. Several patients demonstrated dissociation between the B-LCL-stimulated MLR and mitogen responses. The use of a B-LCL as a stimulator in the MLR is a valuable tool for the assessment of the immune status of patients with a variety of immunodeficiency disorders.

Ataxia Telangiectasia↗