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Biomedical subjects

J A Armstrong

Publications and source records attributed to J A Armstrong.

At least 19 recordsLinked to original sources
PubMed1992

Type I interferons (IFN-alpha and -beta) suppress cytotoxin (tumor necrosis factor-alpha and lymphotoxin) production by mitogen-stimulated human peripheral blood mononuclear cell.

We studied the effect of the different types of interferons on the production of cytotoxin by human peripheral blood mononuclear cells (PBMCs) stimulated with the mitogen phytohemagglutinin (PHA). Maximum secreted levels of cytotoxin were observed at day 3 in culture and consisted of both tumor necrosis factor alpha (TNF-alpha) and lymphotoxin as determined by specific antibodies. Type I interferons (IFN-alpha and IFN-beta) consistently suppressed cytotoxin production. Both TNF-alpha and lymphotoxin were significantly suppressed. Mean suppression by IFN-alpha and IFN-beta (1000 U/ml) was 56 and 66%, respectively, in PBMCs from 18 different donors. The suppressive effects of IFN-alpha and IFN-beta on cytotoxin production were dose responsive over a range of 10 to 1000 U/ml. Type II interferon (IFN-gamma) did not have consistent significant effects. Pretreatment with IFN-alpha or IFN-beta for 24 or 48 h prior to PHA stimulation also resulted in significant suppression. Supplementation with interleukin-2 (10 U/ml) or IFN-gamma (1000 U/ml) did not overcome cytotoxin suppression by IFN-alpha or IFN-beta. Cytotoxin suppression by IFN-alpha and IFN-beta together appeared to be noninteractive. Suppression appeared not to be due to blockade of the cytotoxin release, since both cell-associated cytotoxin and secreted cytotoxin were suppressed to the same level. These results demonstrated that cytotoxin and lymphotoxin production by PHA-stimulated PBMCs could be down-regulated by type I interferons and that there is a substantial difference between the action of type I interferons and type II interferons (IFN-gamma) in modulating the biosynthesis of cytotoxins.

Cells, Cultured↗
PubMed1992

Three neuroblastoma cell lines established from consecutive samples of one patient which show distinct morphologic features, MYCN amplification, and surface marker expression.

Three neuroblastoma cell lines established from tumor samples obtained from one patient are described. The three lines were derived from bone marrow aspirates taken at diagnosis, and 13 and 15 months later. The origin of the cell lines PER-106, PER-107, and PER-108 from malignant neuroblasts was confirmed by electron microscopy studies, surface marker analysis, and assessment of MYCN amplification. Cell lines PER-107 and PER-108, which were established from tumor samples obtained at the time of progressive disease, have significantly shorter doubling times than PER-106 and grow mainly substrate-adherent, while cell line PER-106 (established from sample obtained at diagnosis) consists of small round neuroblastic cells which form large aggregates in suspension culture. The electron microscopy studies revealed distinctive neuroblast-like ultrastructure in all cell lines. The MYCN copy number was amplified (greater than 10 copies) in the established cell lines and in the fresh tumor samples and the relative abundance of MYCN RNA in the cell lines correlated roughly with the extent of the MYCN gene amplification. However, distinct phenotypic differences can be demonstrated among these three lines, which provide a model for the further examination of this highly malignant tumor. Detection of MYCN amplification by chromosomal in situ hybridization was performed on this set of cell lines, as reported by McRobert et al. (this issue, pages 128-134).

Antibodies, Monoclonal↗
PubMed1992

The effect of combinations of ampligen and zidovudine or dideoxyinosine against human immunodeficiency viruses in vitro.

The combinations of ampligen and zidovudine at ratios of 100:1, 25:1, 10:1, and 1:50 acted synergistically to reduce cytopathology caused by HIV in MT-2 cell cultures. Combination indices were less than 1 at all of these ratios representing different combinations of concentrations and at 3 effective doses (ED30, ED50, ED70). Combination of drugs which show synergism at a wide range of ratios of combinations suggest that they may be useful clinically, and that the antiviral efficacy of ZDV may be increased in combination with ampligen. Synergism was also found between ampligen and zidovudine by reduction of HIV-produced plaques in a HeLa cell line expressing CD-4 receptors. However the combination of ampligen and dideoxyinosine against HIV in MT-2 cells was only additive and not synergistic.

Antiviral Agents↗
PubMed1992

Coumarins from Phebalium tuberculosum ssp. megaphyllum and Phebalium filifolium.

A total of 14 coumarins have been isolated from the aerial parts of Phebalium tuberculosum ssp. megaphyllum and 9 from Phebalium filifolium (Rutaceae). Three of the coumarins obtained from P. tuberculosum ssp. megaphyllum are novel and have been characterized, on the basis of spectroscopic analysis, as (E)-7-(6-hydroperoxy-3,7-dimethylocta-2,7- dienyloxy)coumarin [3], (E)-8-(6-hydroperoxy-3,7-dimethylocta-2,7-dienyloxy)psoralen [16] and (E,E)-8-(7-hydroxy-3,7-dimethylocta-2,5-dienyloxy)psoralen [15] In addition, both species yielded the simple acetophenone xanthoxylin, and P. tuberculosum ssp. megaphyllum gave (E)-betulin-3-p-coumarate [20] and (Z)-betulin-3-p-coumarate [21], both of which appear to be novel. The chemotaxonomic implications of coumarin distribution in the two species are discussed.

Chromatography, Liquid↗
PubMed1992

Analysis and examination of cytokine interactions by the median-effect model: an example with antiviral action of tumor necrosis factor and interferon-gamma.

A mathematical model based on the median effect principle was used to demonstrate its usefulness in studying cytokine interactions. The inhibition of cytopathological effects due to encephalomyocarditis virus (EMCV) by interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF) in WISH cells using a microtiter assay was employed. The model was used to analyze the characteristics of the dose-effect relationships of IFN-gamma, TNF, and their combination. The method also was used to define synergism as opposed to additive interaction. This application of the median-effect model proved to be easy and accurate and could be useful in the study of interactions in cytokine research.

Animals↗
PubMed1992

A phase I study of ampligen in human immunodeficiency virus-infected subjects.

Ampligen, poly(I)n:poly(C12U)n, was administered intravenously to 39 human immunodeficiency virus (HIV)-infected subjects, asymptomatic or with early AIDS-related complex (ARC) and with CD4+ cell counts less than 500/mm3 in a phase I dose-escalation study. Six doses ranging from 10 to 570 mg/m2 were administered twice-weekly for 9-25 weeks to groups of 5-7 subjects. There was no significant effect on HIV as measured by serum p24 levels, the proportion of patients from whom HIV could be cocultured from blood, or the concentration of peripheral mononuclear cells positive for the virus. Although patients on 10 and 40 mg/m2 showed a significant decline in CD4+ cell counts, as would be expected in untreated patients, patients who received doses greater than or equal to 120 mg/m2 showed no significant decline in CD4+ cell counts. In addition, there was a significant increase in CD4+ cell counts with respect to dose of ampligen. This effect of ampligen and the fact that it has been shown to act synergistically with zidovudine against HIV in vitro suggest that the combination might be tried clinically in patients.

AIDS-Related Complex↗
PubMed1992

Frequent oropharyngeal shedding of Epstein-Barr virus in homosexual men during early HIV infection.

OBJECTIVE: To determine the frequency of Epstein-Barr virus (EBV) oropharyngeal shedding during HIV infection in homosexual men in the Multicenter AIDS Cohort Study. DESIGN: The cohort consisted of 210 men who were HIV-seronegative at their baseline study visit, 39 of whom seroconverted to HIV at a later date, and 73 asymptomatic and mildly symptomatic men with HIV infection of indeterminate duration. METHODS: EBV in throat washings was detected by transformation of newborn cord blood lymphocytes. RESULTS: EBV was isolated from 49% (35 out of 71) of the HIV-seropositive and 16% (33 out of 204) of the HIV-seronegative homosexual men tested at their baseline visit. Elevated EBV shedding frequency was noted 6 months before, as well as during the first HIV-seropositive clinic visit, in the men who seroconverted to HIV. Seronegative men who shed EBV at their baseline visit seroconverted to HIV within a shorter period than did non-shedders during 5 years of follow-up. Shedding of EBV was not significantly associated with either abnormal T-cell numbers, clinical symptoms or risk for development of AIDS. CONCLUSIONS: There is an increased rate of EBV shedding in HIV-seropositive homosexual men that occurs very early in the course of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Enhanced shedding of cytomegalovirus in semen of human immunodeficiency virus-seropositive homosexual men.

Site-specific shedding of cytomegalovirus (CMV) was assessed in a longitudinal study of homosexual and bisexual men. At initial testing, CMV was cultured from the semen of 33% (19 of 58) of asymptomatic and mildly symptomatic men who were seropositive for human immunodeficiency virus (HIV) at the time of entry into the study, whereas it was cultured from the semen of 17% (10 of 58) of the men who were HIV seronegative. CMV was isolated much more frequently from semen than from urine or throat washing specimens, and it was rarely recovered from stool or blood, regardless of the subject's HIV serostatus. CMV was cultured from the semen of 31% (16 of 52) of the men relatively early after seroconversion to HIV (mean, 12.8 months). CMV was persistently isolated from the semen of a greater proportion of the HIV-seropositive men than from the semen of the HIV-seronegative men during a 4.5-year follow-up period (52 of 110 - [47%] and 15 of 58 [26%] men, respectively). There was an increased relative risk for shedding of CMV in semen in association with decreased CD4+ cell numbers and increased levels of serum immunoglobulin A. However, there was no association of CMV shedding with an increased risk for the development of AIDS.

Adolescent↗
PubMed1991

Zidovudine therapy is associated with an increased capacity of phytohemagglutinin-stimulated cells to express interleukin-2 receptors. Pittsburgh AIDS Clinical Trial Unit.

Zidovudine therapy of AIDS patients has been shown to cause only transient improvements in the numbers of circulating CD4+ cells and the in vitro functional activities of cultured lymphocytes. The present studies were undertaken to determine whether prolonged zidovudine therapy enhanced reactivity in two sensitive assays of T-cell function: the ability of phytohemagglutinin (PHA)-stimulated cells to form T-cell colonies and their capacity to express receptors for the growth factor interleukin-2 (IL-2). Treated patients, studied over periods of 20-60 weeks, showed no improvement in colony formation at any time interval, even in plates supplemented with exogenous IL-2. However, mitogen-stimulated T lymphocytes showed a significant increase in the capacity to express IL-2 receptors (CD25). This enhanced expression resulted primarily from activation of the CD8+ cell subset.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Influence of soluble haemagglutinins on adherence of Helicobacter pylori to HEp-2 cells.

In a study of six laboratory strains of Helicobacter pylori, two different modes of bacterial adherence to HEp-2 cells were found. Electronmicroscopy revealed that strains known to possess soluble haemagglutinin adhered intimately to the cell surfaces, with cupping of the plasma membrane and coalescence of glycocalyces at sites of attachment. Strains of H. pylori without soluble haemagglutinin also attached, but did not induce membrane cupping or show glycocalyx fusion. Light microscopy did not distinguish between these patterns of adherence. Bacterial attachment was unaffected by pre-treatment of HEp-2 cells with neuraminidase. Exposure of the bacteria to trypsin or to colloidal bismuth subcitrate (CBS) before being added to HEp-2 cells markedly impaired bacterial adherence. This effect of CBS may contribute to the known efficacy of bismuth therapy in patients with H. pylori-related gastritis.

Bacterial Adhesion↗
PubMed1991

Hydroxyapatite crystals are a frequent finding in osteoarthritic synovial fluid, but are not related to increased concentrations of keratan sulfate or interleukin 1 beta.

Synovial fluid (SF) was obtained from 40 patients with varying grades of osteoarthritis (OA) of the knee and examined by transmission electron microscopy to ascertain how frequently hydroxyapatite crystals (HA) were present and whether they were related to disease severity or putative markers or promoters of cartilage resorption. HA crystals were conspicuous and abundant in specimens from 21 of the 40 patients studied. Patients in whom HA was present had significantly larger effusions (13.0 +/- 8.9 vs 8.7 +/- 6.1 ml, p less than 0.05). They also tended to have radiologically more severe disease (radiological grade: 2.91 +/- 0.92 vs 2.39 +/- 0.85, p = 0.056). No difference in keratan sulfate (KS) concentrations was observed. Moreover, despite the presence in some specimens of numerous free histiocytes which were actively phagocytosing HA aggregates, the concentrations of interleukin 1 beta (IL-1 beta), a monocyte product with cartilage and bone resorbing activity, were below the limit of detection (20 pg/ml). Our results confirm that HA crystals are a common finding in patients with OA of the knee and show that HA is associated with larger effusions, but not increased SF concentrations of cartilage proteoglycan substituents (KS) or IL-1 beta.

Aged↗
PubMed1990

Epidemiology of genital herpes in Pittsburgh: serologic, sexual, and racial correlates of apparent and inapparent herpes simplex infections.

Women attending family planning clinics in western Pennsylvania were enrolled into a prospective epidemiologic study of herpes simplex virus (HSV) infection. Detection of antibodies to HSV-1 and HSV-2 was based on an immunodot assay using type-specific glycoproteins gG-1 and gG-2. Serologic and historical data at enrollment were analyzed for 4527 subjects; the seroprevalence of HSV-2 was 21.6%. By multivariate analysis, HSV-2 infection as determined by seroprevalence was significantly and independently associated with age, years of sexual activity, race, one or more episodes of other genital infections, lower annual family income, and multiple sexual partners. The presence of antibody to HSV-1 was associated with a lower frequency of antibody to HSV-2, suggesting that developed immunity to HSV-1 protected against HSV-2 infection. Of 926 participants who had antibody to HSV-2, only 117 (12.6%) reported a history of genital herpes. Hence the vast majority of HSV-2 infections were inapparent. Although seroprevalence of HSV-2 was higher among black (35.4%) than white (18.5%) women, black women appeared to have significantly less symptomatic genital herpes than white women (7.7% vs. 14.7%, P less than .01).

Adolescent↗
PubMed1990

Vesicular changes in the myopathies of AIDS. Ultrastructural observations and their relationship to zidovudine treatment.

Six patients with AIDS and AIDS related complex (ARC) who developed neuromuscular symptoms associated with vesicular changes in muscle fibres are reported. Two patients in the advanced stages of AIDS, who did not receive zidovudine, developed proximal limb weakness and wasting: both had a necrotising myopathy with an unusual segmental vesicular change of myofibres. There were numerous vesicles 0.1 to 2 microns in diameter produced by dilatations of the sarcoplasmic reticulum in fibres depleted of myofibrils. Four patients developed a myopathy while receiving zidovudine for AIDS. One of these had an inflammatory myopathy which showed the development of vesicular change due to enlargement and electron lucency of mitochondria. The three other patients with ARC developed muscle pains or weakness and elevated serum CK while on zidovudine. These patients also showed vesicular changes due to enlargement and electron lucency of mitochondria associated with disruption of sarcomeres and the presence of cytoplasmic bodies. The muscular symptoms resolved when ziduvodine was stopped and repeat biopsy in one case revealed no abnormalities.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Relation of alpha and gamma interferon levels to development of AIDS in homosexual men.

Homosexual men who were human immunodeficiency virus (HIV) seropositive at enrollment into the Pittsburgh portion of the Multicenter AIDS Cohort Study had elevated titers of serum alpha and gamma interferon (IFN) within 24 months prior to development of AIDS. In contrast, subjects who developed AIDS relatively early after seroconversion to HIV during this study did not have increased levels of alpha or gamma IFN.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Neutralizing antibody to herpes simplex in pregnant women and their neonates.

The neutralizing antibody (NAb) titer against herpes simplex virus (HSV) was determined in blood obtained at term delivery in 76 women with documented genital HSV infection. Maternal and cord blood NAb titers against HSV-1 and HSV-2 displayed significant correlation (r = .88 and r = 0.89, respectively). In 33% of the paired samples, the neonatal NAb titer against HSV-1 exceeded the concomitant maternal titer, and in 59% the maternal and neonatal NAb titers against HSV-1 were equal. In 28% of the pairs, neonatal NAb titer against HSV-2 exceeded the concomitant maternal NAb titer against HSV-2, and in 59% the neonatal and maternal titers against HSV-2 were equal. Since maternal NAb titers against HSV accurately predict a minimum neonatal NAb titer against HSV-1 and HSV-2 in 92% and 87% of cases, respectively, such measurements may be useful in the management of delivery in women with recurrent genital HSV infection.

Antibodies, Viral↗
PubMed1979

Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root.

Microneurosurgical procedures on the trigeminal-nerve root are often followed by reactivation of herpes simplex virus infection, manifested by herpes labialis or oropharyngeal herpesvirus shedding or both. In a double-blind study of the ability of human leukocyte interferon to prevent this reactivation, patients with a history of herpes labialis were given 7 x 10(4) U of interferon per kilogram of body weight per day or placebo for five days beginning on the day before operation. In 18 patients treated with placebo, herpes labialis developed in 10, and virus shedding in the oropharynx in 15. In 19 patients treated with interferon, lesions developed in five, and shedding in eight. The frequency of reactivation as measured by lesions or positive throat cultures or both was significantly reduced by interferon (P less than 0.05). Of 127 daily throat-wash cultures in the placebo group, 42 per cent were positive for herpesvirus, but of 134 in the interferon group, only 9 per cent were positive (P less than 0.001). We conclude that interferon at a well-tolerated dosage reduces reactivation of latent herpes simplex virus infection after a potent operative stimulus.

Clinical Trials as Topic↗
PubMed1979

Blood levels after sublingual nitroglycerin.

Pharmacokinetic analysis of nitroglycerin (GTN) has been hampered by the lack of a sensitive and specific method for measuring GTN in blood. Therefore, we examined the appearance of GTN in blood after administering 0.6 mg sublingually in 10 studies of normal volunteers. We used a gas-liquid chromatographic method with electron-capture detection and isosorbide dinitrate as the internal standard. GTN appeared in blood at 0.5 minutes, reached a peak of 2.3 +/- 0.36 ng/ml at 2 minutes, fell to 50% of peak value at 7.5 minutes and was barely detectable at 20 minutes. These blood levels paralleled the changes in heart rate and systolic blood pressure. These data show rapid appearance and disappearance of GTN from blood after sublingual administration, a large volume of distribution, and a rapid rate of total body clearance that precludes the liver from being the sole elimination site. This method for analysis of GTN and isosorbide dinitrate should be helpful in defining the role of chronic nitrate therapy.

Adult↗