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Biomedical subjects

J L Sullivan

Publications and source records attributed to J L Sullivan.

At least 163 records · Page 9Linked to original sources
PubMed1989

Characterization of the T cell-mediated cellular cytotoxicity during acute infectious mononucleosis.

Primary infection with EBV during acute infectious mononucleosis (IM) is associated with a cytotoxic response against allogeneic target cells. C depletion with anti-CD3 (OKT3) and anti-CD8 (OKT8) mAb decreased the allogeneic cytolysis of two EBV-infected lymphoblastoid cell lines (LCL) by 96% and 89%, respectively. Complement depletion with the NK cell-specific mAb Leu-11b and NKH-1a resulted in only a slight decrease (less than 35%) in the lysis of these LCL. mAb inhibition studies with OKT3 and OKT8 inhibited the allogeneic lysis of two LCL by 87% and 82%, respectively. The alloreactive cytotoxic response was strongly inhibited by mAb specific for MHC class I determinants (W6/32, 65% inhibition and BBM.1, 58% inhibition). Acute IM lymphocytes lysed the allogeneic EBV-negative cell lines HSB2 (45%) and HTLV-1 T cell lines (16%). NK cell-depleted lymphocytes from an acute IM patient demonstrated preferential lysis of K562 transfected with human HLA-A2 (73%) compared with the K562 transfected control (20%). Cold target competition studies with allogeneic and autologous target and competitor LCL demonstrated no significant competitive inhibition between allogeneic and autologous cells. We interpret these results as evidence that 1) the acute IM-alloreactive cytotoxic response is mediated primarily by CTL; 2) these alloreactive CTL lyse allogeneic target cells irrespective of EBV antigenic expression; 3) MHC class I expression is sufficient for allogeneic recognition and lysis of target cells; 4) distinct effector CTL populations mediate lysis of autologous and allogeneic target cells; and 5) during acute IM, EBV infection results in the induction of both virus-specific and alloreactive CTL populations.

Acute Disease↗
PubMed1989

Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies.

Conventional clotting factor concentrates have, until recently, been "of intermediate purity," containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Detection of major histocompatibility complex class I-restricted, HIV-specific cytotoxic T lymphocytes in the blood of infected hemophiliacs.

Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.

Antibodies, Monoclonal↗
PubMed1989

Soluble CD8 during T cell activation.

The CD8 Ag has long been used as a surface marker for the identification of cytotoxic and suppressor cells. Recently CD8-positive cells have been shown to release a soluble form of the CD8 Ag. We have devised a sandwich monoclonal enzyme immunoassay for the quantitation of this released CD8. Soluble CD8 was released in response to lymphocyte activation. In vitro, PHA or anti-CD3 mAb-mediated T cell activation led to release of CD8 into the culture supernatant. In vivo, serum from patients with EBV-induced infectious mononucleosis (IM), a disease associated with intense CD8+ T cell activation, demonstrated elevations in soluble CD8 (7939 U/ml, day 0) compared to serum from normal controls (289 U/ml). Levels of soluble CD8 correlated (r = 0.82, p less than 0.001) with the increased percentage of CD8+/HLA-DR+ (activated CD8+ T cells) observed in acute IM. Sequential analysis of serum during the course of IM shows that soluble CD8 levels parallel the decline in CD8+/HLA-DR+ cells that occurs with the resolution of the disease. These data suggest that released CD8 may be of value in monitoring the involvement of CD8+ T cells in response to a pathologic event. The functional role of the released CD8 molecule will require further investigation.

Adolescent↗
PubMed1989

Mapping the mutation causing the X-linked lymphoproliferative syndrome in relation to restriction fragment length polymorphisms on Xq.

The X-linked lymphoproliferative syndrome (XLP) results in fatal infectious mononucleosis, hypogamma-globulinemia, and malignant lymphoma. The mutation has been mapped relative to several restriction fragment length polymorphism (RFLP) markers in the Xq21-Xq27 vicinity. The DXS37 locus was found to be near both the DXS42 and XLP loci.

Chromosome Mapping↗
PubMed1989

Arrangement of repetitive sequences in the genome of herpesvirus Sylvilagus.

Herpesvirus sylvilagus is a lymphotropic (type gamma) herpesvirus of cottontail rabbits (Sylvilagus floridanus). Analysis of virion DNA of herpesvirus sylvilagus has revealed that the genome consists of one stretch of about 120 kilobase pairs of internal, unique DNA flanked by a variable number of 553-base-pair tandem repeats. The G + C content of the repetitive DNA is extremely high (83%), as determined by sequencing. The organization of the herpesvirus sylvilagus genome is, therefore, similar to that of the primate lymphotropic viruses herpesvirus saimiri and herpesvirus ateles.

Base Sequence↗
PubMed1989

Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera.

Antibody-dependent cell-mediated cytotoxicity (ADCC) specific for human immunodeficiency virus (HIV) has been described for HIV-infected individuals. To determine the antigenic specificity of this immune response and to define its relationship to the disease state, an ADCC assay was developed using Epstein-Barr virus-transformed lymphoblastoid cell line targets infected with vaccinia virus vectors expressing HIV proteins. The vaccinia virus vectors induced appropriate HIV proteins (envelope glycoproteins gp160, gp120, and gp41 or gag proteins p55, p40, p24, and p17) in infected lymphoblastoid cell lines as demonstrated by radioimmunoprecipitation and syncytia formation with c8166 cells. Killer cell-mediated, HIV-specific ADCC was found in sera from HIV-seropositive but not HIV-seronegative hemophiliacs. This HIV-specific response was directed against envelope glycoprotein but was completely absent against target cells expressing the HIV gag proteins. The ADCC directed against gp160 was present at serum dilutions up to 1/316,000. There was no correlation between serum ADCC titer and the stage of HIV-related illness as determined by T-helper-cell numbers. These experiments clearly implicated gp160 as the target antigen of HIV-specific ADCC activity following natural infection. Vaccines which stimulate antibodies directed against gp160, which are capable of mediating ADCC against infected cells, could be important for protection against infection by cell-associated virus.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

X-linked lymphoproliferative syndrome.

The X-linked lymphoproliferative (XLP) syndrome is characterized by a selective immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. Prospective studies in males prior to EBV infection have demonstrate vigorous cytotoxic cellular responses, which are predominantly polyclonally activated alloreactive cytotoxic T cells. Cytotoxic T cells that recognize EBV-infected autologous B cells have been demonstrated. Fatal EBV infections in males with XLP usually result from extensive liver necrosis. Males who survive acute EBV infection demonstrate global cellular immune defects with deficient T-, B- and NK-cell responses. It is hypothesized that uncontrolled alloreactive T-cell responses triggered by EBV-transformed B cells result in the immunopathy of XLP. Genetic studies have demonstrated XLP to be genetically linked to restriction fragment length polymorphisms detected with the DXS42 and DXS37 probes (from Xq26-q27). These probes make detection of carrier females and presymptomatic (EBV-seronegative) XLP males possible. Treatment of males with XLP experiencing acute EBV infection has not been successful, and current efforts are directed at prophylaxis with intravenous gammaglobulin.

Female↗
PubMed1989

Adriamycin response of two human tumor xenografts using a double-radiolabel organ culture method.

A double-radiolabel method of quantitating drug response in a simple organ culture system was used to study the effects of adriamycin on two human tumor xenografts in vitro. Explants of X56, an adenocarcinoma of colon, and HXG2, an amelanotic melanoma, both maintained by serial transplantation in athymic mice, were sequentially incubated in vitro with 14C-thymidine, one of several concentrations of adriamycin, and then 3H-thymidine. The ratios of second to first radiolabel incorporation declined as a function of adriamycin concentration. HXG2 was significantly more responsive to adriamycin than X56 in the double-radiolabeled assay. Greater sensitivity of HXG2 was confirmed by three additional methods: The human tumor stem cell assay (HTSCA), chemotherapy trials in tumor-bearing athymic mice, and a double-radiolabel protocol in vivo in tumor-bearing athymic mice. An organ culture method of this type may be useful in screening individual patients' tumors for drug resistance.

Adenocarcinoma↗
PubMed1988

Myocarditis presenting as acute myocardial infarction.

Ten patients with acute myocarditis, who were initially seen with clinical signs of acute myocardial infarction, will be discussed. All had symptoms and seven had laboratory evidence of an acute viral infection. Acute cardiac findings consisted of chest pain in nine patients, compatible ECGs and elevated creatine kinase levels in 10, positive MB fractions in eight, and regional wall motion abnormalities in eight. Acutely, the left ventricular ejection fraction was less than 55% in six patients; ventricular ectopy occurred in five patients, bundle branch block in four, transient junctional escape rhythm in three, and congestive heart failure in three. Among the nine patients followed-up for 1 to 14 months there was one death, five patients had normal results of exercise tests, and three had normal coronary angiograms. Wall motion abnormalities persisted in four patients; ejection fraction improved in five and was less than 55% in three. These findings suggest that focal myocardial damage may occur during acute viral myocarditis and mimic acute myocardial infarction resulting from atherosclerotic coronary artery disease.

Adult↗
PubMed1988

Serum antioxidant activity in neonates.

Antioxidant activity was measured in cord sera from 25 infants whose birth weights ranged from 830 to 3700 g. Antioxidant activity showed a significant positive association with birth weight. Deficiency in serum antioxidant activity may be important in the pathogenesis of certain neonatal disorders such as retinopathy of prematurity.

Adult↗