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W P Parks

Publications and source records attributed to W P Parks.

At least 37 records · Page 2Linked to original sources
PubMed1988

Statistical methods for the analysis of HIV-1 core polypeptide antigen data in clinical studies.

Levels of HIV-1 core polypeptide were assessed in serum and in lymphocyte cultures obtained from ARC and AIDS patients enrolled in a prospectively randomized, placebo-controlled study of zidovudine (AZT). Because these data have special features uncharacteristic of most laboratory data, a comprehensive account of statistical methods appropriate for their analysis is contained in this paper. Standard methods are described for the analysis of HIV-1 antigen in serum collected repeatedly over time in the same individual. For the analysis of lymphocyte culture data, more sophisticated statistical techniques based on nonparametric survival analysis methods are proposed. Using microcomputer software available upon request and developed to implement this statistical procedure, a significant decline in lymphocyte HIV-1 virus expression was noted between pretreatment and 3 months after the initiation of therapy among AZT-treated patients (p = 0.0017) that was not seen in placebo-treated patients (p = 0.25). Statistically significant between-group differences were also noted in the change from baseline at 3 months in HIV-1 antigen serum data (p = 0.040). We conclude that HIV-1 core polypeptide is an important measure of the antiretroviral activity of AZT and that the demonstrated clinical efficacy of AZT relative to placebo parallels its antiretroviral effect.

AIDS-Related Complex↗
PubMed1988

HIV-1 inhibition by azidothymidine in a concurrently randomized placebo-controlled trail.

Two independent measures of human immunodeficiency virus type 1 (HIV-1) infection, virus isolation, and serum levels of p24 antigen were evaluated in a double-blind randomized clinical trial of the safety and efficacy of a nucleoside analogue, 3'-azido-3'-deoxythymidine (AZT) versus placebo in a single center. Pretreatment studies from 38 AIDS and AIDS-related complex (ARC) patients were comparably positive for virus isolation from their lymphocytes; all patients were qualitatively virus positive. Before AZT treatment, there was significantly decreased virus recovery in patients with higher numbers of CD4-positive lymphocytes. Within 1 month of AZT therapy, the time in culture required to register virus positivity was increased markedly in the AZT-treated group, and over the following several months progressive diminution in virus recovery was noted. Similar changes were not seen in patients concurrently receiving placebo treatment. Before treatment, 16 of 20 and 12 of 16 patients in the AZT and placebo groups, respectively, were p24 antigen positive. Marked reduction in serum p24 levels were noted in 11 of 16 (69%) of the p24 antigen-positive AZT-treated patients compared to 3 of 12 (25%) of the p24 antigen-positive placebo-treated patients (p = 0.02). There was a marked virologic response in 14 of 20 (70%) of the AZT-treated patients compared to 4 of 18 (22%) placebo-treated patients (p = 0.004). A higher frequency of positive clinical and immunological effects also were noted in the AZT-treated patients relative to placebo-treated patients (p = 0.02 and p = 0.06, respectively).

Acquired Immunodeficiency Syndrome↗
PubMed1987

Simultaneous infections with human T cell leukemia virus type I and the human immunodeficiency virus.

Four adults form four separate households were found to have simultaneous retroviral infections with human T cell leukemia virus type I (HTLV-I) and human immunodeficiency virus (HIV). These individuals were seropositive for the HTLV-I env transmembrane protein p21E, and all had antibodies to the HTLV-I core polypeptide p24. All four patients also had antibodies to the HIV env transmembrane polypeptide p41E and to the HIV core polypeptide p24. HTLV-I was isolated from peripheral blood lymphocytes of all four individuals, and both viruses were isolated from two of them. Evidence of HIV transmission was noted in the family contacts. Eight of 10 children of these four adults were seropositive for HIV, presumably because of perinatal transmission from infected mothers. Two of five spouses of these adults were examined; these spouses had antibodies to HIV and were positive for virus. No evidence of HTLV-I transmission was noted in these families.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Human retroviral env and gag polypeptides: serologic assays to measure infection.

Humoral antiviral responses to human retrovirus infections identify persistently infected individuals and can be used to characterize virus-host interactions. Antibodies to native viral polypeptides have been reliably measured, although quantitation of env antibodies is difficult due to a lack of purified antigens. To quantitate antibodies to env antigens, bacterially expressed cloned env polypeptides from the transmembrane regions of human T lymphotropic virus types I and III were applied to nitrocellulose filters in an immunodot assay. A combination of the sensitivity of the Western blot procedure and the specificity of peptides from defined viral sequences was used to detect 49/49 HTLV-III/LAV-infected individuals previously defined as seropositive by radioimmunoprecipitation sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Of these HTLV-III/LAV envelope seropositive people, 22% lacked antibody to p24 in a radioimmunoassay. In contrast, the sensitivity of antibody detection to HTLV-I env antigens and p24 were comparable. Antibodies to HTLV-I and HTLV-III/LAV env transmembrane peptides were not cross-reactive. Levels of antibody to env antigens of both HTLV-I and HTLV-III/LAV persisted without change for at least 26 mo, suggesting that most infections represent stable virus-host interactions. The use of bacterially expressed env peptides offers a rapid serologic approach for distinguishing human retroviral infections and can be used to define immune responses to specific regions of the viral genome.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS.

In a study of genetic variation in the AIDS virus, HTLV-III/LAV, sequential virus isolates from persistently infected individuals were examined by Southern blot genomic analysis, molecular cloning, and nucleotide sequencing. Four to six virus isolates were obtained from each of three individuals over a 1-year or 2-year period. Changes were detected throughout the viral genomes and consisted of isolated and clustered nucleotide point mutations as well as short deletions or insertions. Results from genomic restriction mapping and nucleotide sequence comparisons indicated that viruses isolated sequentially had evolved in parallel from a common progenitor virus. The rate of evolution of HTLV-III/LAV was estimated to be at least 10(-3) nucleotide substitutions per site per year for the env gene and 10(-4) for the gag gene, values a millionfold greater than for most DNA genomes. Despite this relatively rapid rate of sequence divergence, virus isolates from any one patient were all much more related to each other than to viruses from other individuals. In view of the substantial heterogeneity among most independent HTLV-III/LAV isolates, the repeated isolation from a given individual of only highly related viruses raises the possibility that some type of interference mechanism may prevent simultaneous infection by more than one major genotypic form of the virus.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS.

To determine the extent and nature of genetic variation present in independent isolates of HTLV-III/LAV, the nucleotide sequences of the entire envelope gene and parts of gag and pol were determined for two AIDS viruses. The results indicated that variation throughout the viral genome is extensive and that the envelope gene in particular is most highly variable. Within the envelope, changes were most prevalent within the extracellular region where clustered nucleotide substitutions and deletions/insertions were evident. Based on predicted secondary protein structure and hydrophilicity, these hypervariable regions represent potential antigenic sites. In contrast to the hypervariable regions, other sequences in the extracellular envelope and the overall envelope structure (including 18 of 18 cysteine residues), as well as most of the transmembrane region, were highly conserved.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Dependence of initiation of an innocent bystander cytotoxicity reaction on the association of viral antigens and tumor cell membranes in mice.

In chemically induced mouse mammary tumors in BALB/c mice, no murine mammary tumor virus (MuMTV) antigens could be detected in the tumor cell membranes. In contrast, in mammary tumors of spontaneous appearance in BALB/cfC3H mice neonatally infected with MuMTV, viral antigens could be detected by immunofluorescence. Specific activation of immune spleen lymphocytes in vitro by homologous tumor cell membrane preparations resulted in an innocent bystander cytotoxicity reaction in BALB/c mice bearing either the chemical- or virus-induced mammary tumors. Non-tumor bearers did not respond in this reaction. The cytotoxicity effector cell was a nylon-adherent Thy 1.2+, Lyt 1+, Lyt 2+ lymphocyte. Induction of the reaction in the chemically induced mammary tumor bearers was related to tumor-associated antigens, but in the mice with MuMTV-induced tumors, it was possible that all responses were solely due to viral antigens. Biochemical analyses using immunoprecipitation techniques indicated that the major external glycoprotein of MuMTV (gp52) was present in the tumor cell membrane preparations. Preincubation of the cell membranes of virus-induced tumors with anti-MuMTV completely blocked the capacity of this preparation to induce the cytotoxicity. Preabsorption of the anti-MuMTV with purified MuMTV removed all the blocking activity of these sera, indicating that the antigenic determinants recognized were of viral origin. However, purified MuMTV failed by itself to elicit the innocent bystander cytotoxicity. This observation indicates that an association with membranes was necessary for the viral antigens to initiate and/or effect this cell-mediated immune reaction.

Animals↗
PubMed1985

Mothers of infants with the acquired immunodeficiency syndrome. Evidence for both symptomatic and asymptomatic carriers.

Sixteen mothers of 22 infants with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were followed up for evidence of clinical and immunologic abnormalities. With one exception, all mothers were clinically well at delivery but had evidence of immune dysfunction, with T-cell abnormalities and inverted T4/T8 ratios and/or elevation of serum immunoglobulin levels, particularly of IgG. During a follow-up period that averaged 30 months, AIDS developed in five of the mothers and AIDS-related complex in seven. Twelve subsequent pregnancies in 11 mothers produced four affected infants, suggesting that mothers can be persistently infected. Six mothers were delivered of subsequent infants who remain unaffected. These results suggest that the mothers are the likely source of infection in non-transfusion-associated cases of AIDS or AIDS-related complex in infants, that mothers have persistent immunologic abnormalities, and that they are at increased risk of developing AIDS or AIDS-related complex.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Acquired immunodeficiency syndrome in infants.

Fourteen infants with clinical and laboratory features of an acquired immunodeficiency syndrome were identified in a single metropolitan area from November 1980 to July 1983. Patients were predominantly of Haitian parentage, although two cases occurred in offspring of non-Haitian intravenous drug abusers. Only one patient had received a blood transfusion before the development of clinical findings. The predominant clinical findings included failure to thrive, persistent infection of the oral mucosa by Candida albicans, chronic pulmonary infiltrates, hepatosplenomegaly, lymphadenopathy, and diarrhea. Immunologic studies showed most of the infants to have inverted ratios of T-cell subsets, greatly increased immunoglobulin levels, and circulating immune complexes. Lymphopenia was not common, as it is in adult patients. Infectious agents responsible for opportunistic infections in this series included Pneumocystis carinii, herpesviruses, particularly cytomegalovirus, and C. albicans. Bacterial infections were common, and gram-negative sepsis was the major cause of death in the seven infants who have died. At autopsy, two infants had disseminated lymphadenopathic Kaposi's sarcoma. These observations suggest the likelihood of transplacental, perinatal, or postnatal transmission of an as yet unidentified infectious agent that causes this disease.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Expression and demethylation of germinally-transmitted BALB/c mouse mammary tumor virus DNA in Abelson MuLV B-lymphoid cell lines.

Murine mammary tumor virus (MMTV) RNA expression, DNA organization and DNA demethylation were examined in BALB/c B-lymphoid cell lines produced by transformation with the Abelson murine leukemia virus (AbMuLV). The MMTV DNA sequences in AbMuLV B cell lines, based on restriction mapping with EcoRI, PstI, BglII, BamHI and SacI and molecular hybridization with cloned probes of the MMTV LTR, gag-pol or env gene regions, were identical to the germinally-transmitted MMTV DNA complement of BALB/c mice. Several AbMuLV B cell lines expressed MMTV poly(A+)-RNA at detectable levels. MMTV poly(A+)-RNA for the env gene, 3.8 kb, and the long terminally redundant (LTR) region, 1.7 kb, were detected in some AbMuLV B cell lines. MMTV DNA sequences in the AbMuLV B cell lines were at least partially sensitive to digestion by the methylation-sensitive restriction endonucleases HhaI and HpaII. HhaI-sensitive sites were present in Units I, II and III of the germinally-transmitted MMTV DNA and were localized specifically near the 5' end of the 5' and 3' LTRs of both Units II and III. HpaII-sensitive sites were localized near the 3' end of the 3' LTRs of Units II and III, and at a cellular site 2.1 kbp 5' to the 5' LTR. These observations demonstrate that the germ line MMTV DNA sequences of BALB/c mice are expressed in cells of B lymphocyte origin, and suggest a correlation between MMTV RNA expression and selective demethylation in the LTR regions of germinally-transmitted MMTV DNA sequences.

Abelson murine leukemia virus↗
PubMed1984

Antigenic determinants in a virus-induced mouse mammary tumor recognized by cell-mediated immune assays.

Purified tumor cell membrane (PTCM) fractions from spontaneous BALB/cfC3H mammary adenocarcinomas elicit blastogenic responses in spleen cells of tumor-bearing mice. Previous studies have demonstrated that splenic T-cells are the major responding cell population but have not clarified whether the antigens responsible for the reactions are exclusively viral in origin or may involve nonviral tumor-associated antigens (TAA). Pretreatment of PTCM preparations with polyvalent anti-murine mammary tumor virus (MuMTV) completely obliterated the ability of PTCM to stimulate an innocent bystander cytotoxicity reaction; however, it reduced the blastogenic response by only 60%, suggesting that the two assays may measure different antigenic reactivities. The specificity of the anti-MuMTV blocking for viral antigens was demonstrated by the complete absorption of the serum-blocking reaction with purified MuMTV particles in the cytotoxicity assay; however, absorption was only partial in the blastogenesis assay. Incubation with purified Rauscher murine leukemia virus particles failed to absorb the neutralizing effect of the sera. These data suggest that putative TAA can be detected in the blastogenesis assay but not in the cytotoxicity reaction. Ammonium sulfate-precipitated immunoglobulin fractions of sera from tumor-bearing BALB/cfC3H mice (TBMS) completely blocked the stimulatory potential of PTCM in both the blastogenesis and the cytotoxicity assays. In the reciprocal experiment to that described above, preabsorption of TBMS immunoglobulins with purified MuMTV completely removed the inhibition of the cytotoxicity but again only partially restored the blastogenic response. The reaction could be completely restored by preabsorption of TBMS with PTCM. These results support the contention of nonvirion antigen involvement in the blastogenesis reaction. In conclusion, these two assay systems detect different antigenic determinants on the MuMTV-expressing tumor cell membranes. Both viral and other antigens appear to be relevant in this model system, and serum factors present in the immunoglobulin fractions of tumor-bearing mice can inhibit T-cell responses directed at either kind of antigenic moieties.

Adenocarcinoma↗
PubMed1981

Lymphoproliferative responses to mouse mammary tumor virus in lymphocyte subsets of breast cancer patients.

Altered immunologic reactions were observed in breast cancer patients as compared to those in normal subjects. Lymphoproliferative responses to murine mammary tumor virus (MuMTV) were significantly enhanced in peripheral blood mononuclear cells from patients with metastatic disease. These reactivities occurred with mammary tumor virus purified from either mouse milk or infected feline kidney cells but not with Rauscher murine leukemia virus. For the assessment of the role of peripheral blood mononuclear leukocyte subpopulations in the responsiveness to MuMTV, the cell preparations were fractionated according to their ability to form spontaneous rosettes with sheep red blood cells (E-rosettes). The effectiveness of the separation was ascertained by means of cell surface markers, i.e., presence of surface immunoglobulins or a T-cell marker. Leu-1 antigen, and mitogen-induced blastogenesis. The responsiveness to the MuMTV antigen(s) was associated with the T-cell subset, identified as the E-rosetting. Leu-1-positive, and surface immunoglobulin-negative population. Although some subjects with the normal population gave positive reactions, the results reveal an apparent association between high levels of responsiveness to MuMTV within the T-lymphocyte subset and breast cancer disease.

Antigens, Viral↗