PubMed Health⌕ Search

Biomedical subjects

L E Adams

Publications and source records attributed to L E Adams.

At least 19 recordsLinked to original sources
PubMed1998

Genetic and immunologic studies of patients on procainamide.

Forty (40) patients with cardiac arrhythmias receiving procainamide (PA) therapy and 24 patients who were receiving other drugs for their cardiac disorders were investigated for class II HLA phenotypes and their DRB1*04 and DQB1*03 subtypes. Other genetic marker evaluations in the PA patients included: 1) class III MHC C4A and C4B null alleles of complement; and, 2) acetylation phenotype. Twenty (20) of the PA patients were also tested for the ability of their stimulated cells to secrete Interleukin-1 (IL-1 beta) and tumor necrosis factor (TNF alpha). We also examined the spontaneous production of these cytokines by peripheral blood leukocytes (PBL) from patients who were receiving chronic PA treatment. The results revealed no association of acetylation phenotypes with the class II HLA phenotypes nor class III MHC C4 allotypes in these patients. The results did show a significant increase in class III C4 complement allotypes in the PA patients when compared to the controls. The results also showed a significant increase in autoantibodies and DQw3 phenotypes in the PA patient group when compared to control populations. Results of spontaneous IL-1 and TNF production suggested there may be an association of select class II HLA phenotypes in some patients and this may be relevant to host responsiveness to PA treatment.

Acetylation↗
PubMed1995

Triplex-DNA stabilization by hydralazine and the presence of anti-(triplex DNA) antibodies in patients treated with hydralazine.

Hydralazine is an antihypertensive drug that elicits andti-nuclear antibodies in patients as an adverse effect. We investigated the ability of hydralazine to promote/stabilize the triplex DNA form of poly(dA).2poly(dT). Under conditions of low ionic strength, the polynucleotide melted as a double helix with a melting temperature (Tm) of 55.3 degrees C. Hydralazine destabilized this duplex form by reducing its Tm to 52.5 degrees C. Spermidine (2.5 microM), a natural polyamine, provoked the triplex form of poly(dA)-.2poly(dT) with two melting transitions, Tm1 of 42.8 degrees C corresponding to triplex-->duplex+single-stranded DNA and Tm2 of 65.4 degrees C, corresponding to duplex melting. Triplex DNA thus formed in the presence of spermidine was further stabilized by hydralazine (250 microM) with a Tm1 of 53.6 degrees C. A similar stabilization effect of hydralazine was found on triplex DNA formed in the presence of 5 mM Mg2+. CD spectra revealed conformational perturbations of DNA in the presence of spermidine and hydralazine. These results support the hypothesis that hydralazine is capable of stabilizing unusual forms of DNA. In contrast with the weak immunogenicity of DNA in its right-handed B-DNA conformation, these unusual forms are immunogenic and have the potential to elicit anti-DNA antibodies. To test this possibility, we analysed sera from a panel of 25 hydralazine-treated patients for anti-(triplex DNA) antibodies using an ELISA. Our results showed that 72% of sera from hydralazine-treated patients contained antibodies reacting toward the triplex DNA. In contrast, there was no significant binding of normal human sera to triplex DNA. Taken together our data indicate that hydralazine and related drugs might exert their action by interacting with DNA and stabilizing higher-order structures such as the triplex DNA.

Adolescent↗
PubMed1994

Role of genetic factors in drug-related autoimmunity.

Although there is evidence to suggest that genetic factors play a major role in the pathogenesis of many of the rheumatic diseases, far less is known of their role in the induction and expression of human autoimmunity resulting from long-term exposure to drugs, chemicals and environmental agents. Pharmacogenetic factors represent an important source of interindividual variation in response to drugs; most research to date has focused on genetic polymorphism of drug metabolism via N-acetylation, S-methylation or cytochrome P-450-catalyzed oxidation. In drug-related autoimmunity, there is limited evidence that the host's genetic background plays a major role beyond the expression of autoantibodies. More recent prospective studies have concentrated on the association of MHC-genes in the expression of autoimmunity and the susceptibility of patients to develop drug-related clinical syndromes.

Acetylation↗
PubMed1994

Paraspinal EMG and autonomic reactivity of patients with back pain and controls to personally relevant stress.

The reactivity of surface paraspinal EMG was contrasted among groups of (1) patients seeking treatment for chronic back pain, (2) nonpatients reporting chronic back pain, and (3) healthy controls. The EMG response to the personally relevant stressor (all stimuli were 1 min.) tasks was greater for the patient group relative to the other two groups. However, the patients' magnitude of response elicited by the control task was nearly equal to that of the personally relevant task, suggesting that the task demand to "describe a recent event" may be the "personally relevant" stressor component rather than the emotional valence attached to the content of that description.

Adult↗
PubMed1993

Hydralazine induces Z-DNA conformation in a polynucleotide and elicits anti(Z-DNA) antibodies in treated patients.

We studied the effect of hydralazine, an antihypertensive drug with lupus-inducing side effects, on the conformation of poly(dG-m5dC).poly(dG-m5dC) and a plasmid with a 23 bp insert of (dG-dC)n.(dG-dC)n sequences. Using an e.l.i.s.a. with a monoclonal anti-(Z-DNA) antibody Z22, we found that hydralazine provoked the Z-DNA conformation in poly(dG-m5dC).poly(dG-m5dC) at 250-500 microM concentration. The supercoiled form of hydralazine-treated plasmid bound to Z22 in a gel-retardation assay. To examine further whether Z-DNA could act as an inciting agent in anti-nuclear antibody production in patients, we analysed 65 sera from 25 hypertensive patients taking hydralazine and found anti-(Z-DNA) antibodies in 82% of these sera. Sera from age-matched normal controls showed no binding to Z-DNA. Data on sera drawn sequentially from four hypertensive patients showed that antibodies were present after the drug treatment. These data demonstrate the presence of a high incidence of anti-(Z-DNA) antibodies in patients treated with hydralazine and suggest that a possible mechanism for the production of autoantibodies in drug-related lupus might involve the induction and stabilization of Z-DNA by drugs.

Acetylation↗
PubMed1993

Study of procainamide hapten-specific antibodies in rabbits and humans.

Procainamide (PA) is the drug most commonly associated with the induction of autoantibodies and drug-related lupus (DRL). While the majority of these patients express autoantibodies, antibodies to the parent drug and metabolites, PA-hydroxylamine (PAHA) or nitroso-PA (NOPA), have not been reported in humans. Hapten-carrier conjugates were prepared using human hemoglobin (HgB) or autologous rabbit erythrocytes with PAHA or NOPA. PA was conjugated to rabbit serum albumin (RSA) or egg albumin (OVA) via diazotization and condensation methods. Rabbits were immunized with hapten conjugates in Freund's adjuvant. These hapten-carrier compounds (5-10 micrograms/ml) were used as test antigens for antibodies in sera from the rabbits and 40 patients on chronic PA treatment. 10 SLE patients, 33 elderly and 20 young normal controls by ELISA. Type I and II collagens were also used as test antigens for human sera. Sera from rabbits immunized with the PA compounds had elevated IgG antibody values to PA, PAHA and NOPA, but no autoantibodies. Absorption of the rabbit sera with the PA compounds reduced the antibody levels; ssDNA and histones failed to inhibit the total binding values. Mean binding to PA-OVA was 0.95 +/- 0.41 for PA patients and 1.37 +/- 0.26 standard error of means (S.E.M.) in the SLE patients compared to 0.37 +/- 0.14 S.E.M. in the normal sera (P < or = 0.05); similar binding values to PAHA-HgB and NOPA-HgB were also observed. Sixty-eight percent of the PA patients had antibodies to type II collagen. Elevated binding values to PA compounds were inhibited by absorption of human sera with ssDNA or total histones; absorption with PA or PAHA had no significant effect. These findings suggest that sera from PA patients containing high titers of autoantibodies cross-react in vitro with unrelated antigens.

Adult↗
PubMed1993

Genetic, immunologic and biotransformation studies of patients on procainamide.

This report represents follow-up observations of a unique long-term study of patients on procainamide (PA) for various cardiac arrhythmias. Serologic and clinical evaluations associated with drug-related autoimmunity were assessed and patients were characterized for factors postulated to influence susceptibility to autoimmunity, including acetylator phenotype, oxidative metabolism of PA, HLA class profile, and production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Fifty-two percent had IgM and 70% IgG antibodies to total histones; 67% had IgG antibodies to histone H2A/H2B. Patients were equally divided between fast and slow acetylators. N-oxidative metabolism of PA was indicated by the presence of urinary nitroprocainamide, which correlated with elevated titers of antihistone antibodies. There was a significant incidence of the DQw7 split of DQw3 in PA patients when compared to controls, and the frequency of antibodies to total histones and H2A/H2B was significantly increased in the DQw7 patients. C4A*QO and C4B*QO alleles were more frequent in the PA patients than in controls. IL-1 and TNF production was not different in patients compared to controls. These data suggest that certain genetic factors may serve as markers for PA-related autoimmunity.

Aged↗
PubMed1992

Serologic evaluation of patients receiving procainamide.

This controlled study examined the characteristics of serologic abnormalities in 52 patients receiving procainamide for cardiac arrhythmias, who had no symptoms of a connective tissue disease. Antinuclear antibodies occurred in 43 patients (83%). Significant elevation of antibody binding to single-stranded DNA (mean +/- SEM 30 +/- 2.6%), double-stranded DNA (13 +/- 1.1%), Z-DNA (optical density 0.54 +/- 0.06), and poly A (7.2 +/- 0.6%) was seen (P less than 0.001). Thirty-four patients (65.4%) had antibodies to total histones, most frequently, the H2A/2B dimer. IgG antibodies to H2A/2B correlated with the cumulative procainamide dose. One patient subsequently developed drug-related lupus.

Aged↗
PubMed1991

A study of nasometric values for normal nasal resonance.

It was the purpose of this study to obtain nasalance values for a large number of normal adult subjects speaking a variety of dialects of English. The Nasometer was used to measure the amount of nasal acoustic energy in the speech of 148 normal adults from four geographical regions of North America. Means and standard deviations for the nasalance and deviation scores are presented for each of three different reading passages. The Mid-Atlantic speakers were found to have significantly higher nasalance scores on all three reading passages. In addition, the female subjects had significantly higher nasalance scores on the Nasal Sentences. These differences are discussed with regard to potential reasons for their existence and implications for understanding velopharyngeal function in normal and abnormal speakers.

Adolescent↗
PubMed1990

Effects of procainamide hydroxylamine on generation of reactive oxygen species by macrophages and production of cytokines.

A series of experiments was conducted to examine the effects of the N-oxidized metabolite of procainamide, procainamide hydroxylamine (PAHA), on reactive oxygen species (ROS) production by macrophages in vitro, as well as on the release of the cytokine interleukin-1 (IL-1). Results with PAHA were compared with those from the parent compound, procainamide, and in some cases with other procainamide metabolites such as N-acetylprocainamide or nitrosoprocainamide. The effects of PAHA on ROS production by mouse and rat macrophages were complex, resulting in both stimulatory and inhibitory activity depending upon the PAHA concentration and whether macrophages were resting or elicited. The primary effect of PAHA appeared to be a stimulation of ROS production. Monocytes pretreated with PAHA (20 microM) depressed the responsiveness of lymphocytes in co-culture to a T-cell mitogen (conconavalin A) but not a B-cell mitogen (lipopolysaccharide). This effect was inhibited when monocyte pretreatment with PAHA was accompanied by the antioxidants, catalase or superoxide dismutase. IL-1 production by rat adherent splenocytes was unaffected by PAHA in concentrations that were not cytotoxic. These observations suggest that the oxidative metabolism of procainamide to PAHA may result in enhanced production of ROS by macrophages contributing its toxicity to lymphocytes.

Animals↗
PubMed1989

Procainamide hydroxylamine lymphocyte toxicity--I. Evidence for participation by hemoglobin.

A number of lines of evidence suggest that the lupus-like symptoms associated with procainamide therapy may be caused by products of metabolic N-oxidation. In the present study, the perfusion of the isolated rat liver with a hemoglobin-free solution containing procainamide (100 microM) resulted in the rapid appearance of the N-oxidation metabolite procainamide hydroxylamine in the perfusate. Addition of procainamide hydroxylamine in vitro to whole rat blood (1-40 microM) resulted in a concentration-dependent loss of proliferative response among mononuclear cells isolated from the treated blood and cultured with mitogens (phytohemagglutinin, PHA-P: concanavalin A, Con A; and pokeweed mitogen, PWM), as well as a loss of viability. Similar effects on lymphocyte mitogen responsiveness were observed when procainamide hydroxylamine (1-40 microM) was added to rat whole splenic cell populations. Carbon monoxide or ascorbic acid pretreatment inhibited the toxicity of procainamide hydroxylamine to lymphocytes in whole blood, but only carbon monoxide pretreatment inhibited procainamide hydroxylamine-induced methemoglobin formation. These observations are consistent with the participation of hemoglobin in a redox cycle with procainamide hydroxylamine, generating products which are primarily responsible for its cytotoxicity in blood.

Acecainide↗
PubMed1989

Immunomodulatory effects of procainamide metabolites: their implications in drug-related lupus.

Evidence suggests that N-oxidized metabolites of procainamide may be responsible for the development of lupus-like symptoms associated with procainamide therapy. The human hepatic microsomal metabolism of procainamide has been previously reported to result in formation of the N-hydroxylamine derivative of procainamide (procainamide hydroxylamine [PAHA]). The objective of this study was to examine the effects of PAHA on human lymphocytes and adherent cells (monocytes and macrophages). When incubated with lymphocytes in whole blood, PAHA enhanced the response to mitogen and immunoglobulin secretion at lower concentrations (less than or equal to 4 mumol/L) but suppressed these functions at higher concentrations. The cytotoxic effects were nonselective for T lymphocytes and B lymphocytes and appeared to involve an interaction between PAHA and hemoglobin. When erythrocytes were removed or when hemoglobin was converted to carboxyhemoglobin, the suppressive effects of PAHA on lymphocytes were reduced. PAHA stimulated interleukin-1 production by adherent cells at 25 mumol/L but had no effect at lower concentrations. Superoxide anion release was unaffected by PAHA in "resting" adherent cells. Pretreatment with PAHA (2 mumol/L) diminished superoxide release in response to stimulation by phorbol myristate acetate (PMA) or latex bead phagocytosis but augmented superoxide release when coincubated with PMA or latex. These observations indicate that PAHA produces complex, concentration-dependent interactions with human immunoregulatory cells, and they suggest that the effects of PAHA on lymphocyte function may result from the further oxidation of PAHA by hemoglobin, perhaps to the nitroso form.

Adult↗
PubMed1988

Acquired immune deficiency syndrome (AIDS) and autoimmunity--mutually exclusive entities?

Loss of normal immune homeostasis occurs in acquired immune deficiency syndrome (AIDS). We evaluated patients at the University of Cincinnati and New York University Medical Centers for serologic evidence of autoimmune changes. Specifically, tests for antinuclear and organ-specific antibodies by immunofluorescence, antisperm and anti-seminal plasma antibodies, rheumatoid factor by latex and sensitized sheep cell agglutination techniques, anti-polyadenosine (poly A), and single-stranded DNA antibodies were performed in human immunodeficiency virus (HIV) antibody-positive sera. A parallel study of mitogen responsiveness was performed and showed inhibition of response by AIDS and AIDS-related complex (ARC) sera. In spite of evidence of polyclonal B-cell activation, hyperglobulinemia, and the presence of antibodies to many infectious agents, as well as the known cellular immune abnormalities, the patients tested had a striking absence of these autoantibodies. The only major difference noted from normal controls, was a low but significant level of antibody binding to poly A. The autoimmune connective tissue diseases were not observed in this group of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Sperm and seminal plasma antibodies in acquired immune deficiency (AIDS) and other associated syndromes.

Although HIV has been established as the etiologic agent in AIDS, other contributory cofactors may be responsible for selective clinical manifestations of the syndrome. While the pathogenesis remains unclear, the development of immunologic abnormalities observed in some homosexual males with AIDS and AIDS-related complex may be attributed to repeated exposure to allogeneic sperm and seminal plasma components. Accordingly, antibody levels to semen fractions were measured in sera from 338 individuals (295 AIDS, 36 ARC, 16 randomly selected homosexuals, 29 patients with infectious hepatitis, 12 hemophiliacs, 20 rheumatic disease patients, and 24 healthy heterosexual adults). The methods were (i) passive hemagglutination for antibodies to human seminal plasma (HuSePl), and (ii) indirect immunofluorescence (IF) assay on methanol-fixed human sperm noting staining of acrosomal, equatorial, postnuclear, and tail main-piece regions. HuSePl was positive in 31% AIDS sera, while 39% were positive by IF. ARC sera were 30% positive for HuSePl and 38% positive IF. No control sera were positive. Results reveal a significant incidence of antibody to sperm and seminal plasma components in ARC and AIDS patients. Because of the known immunomodulating properties of both, it is possible that these responses may indicate risk factors for disease progression and severity.

AIDS-Related Complex↗
PubMed1986

Polynucleotide antibodies in connective tissue disease: viral markers or disease mediators?

Antibodies to polynucleotides are seen primarily in systemic lupus erythematosus (SLE), but also occur in a variety of other connective tissue diseases. We looked at the prevalence of antinucleotide antibodies (double- and single-stranded RNA and DNA [dRNA, sRNA, dDNA, and sDNA]) in the sera of patients with SLE (70), rheumatoid arthritis (RA) (31), juvenile rheumatoid arthritis (JRA) (68), osteoarthritis (12), and of 22 patients with a preceding viral illness. In comparison with sera from a control population, elevated mean antibody levels to sRNA were found in the sera of all the patients with connective tissue disease, as well as in the sera of patients with preceding RNA, but not DNA, viral infections. Elevated mean levels of antibodies to dRNA were seen in all groups with the exception of RA. Elevated mean antibody titers to sDNA were not seen in patients with JRA nor were they present in the sera of patients with preceding RNA viral infections. Elevated mean anti-dDNA titers were seen only in sera from patients with SLE. High correlation coefficients between the levels of antibodies to sRNA and dRNA in sera from SLE and RA, and between sDNA and dDNA in sera from SLE suggest cross-reactivity of the antibodies in these diseases. Immunization of an elderly population with influenza (RNA) viral vaccine induced antibodies to sRNA only. These studies further document the prevalence of antipolynucleotide antibodies in the sera of patients with connective tissue diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Familial alterations of immunoregulation in systemic lupus erythematosus.

To better define the relationship between suppressor cell function and number and disease expression, the immunoregulatory profiles of 12 probands with systemic lupus erythematosus (SLE) and 34 of their asymptomatic family members were studied, using concanavalin A induced suppressor cells for functional analysis. SLE family members as a whole showed no impairment of mean suppressor levels, although 7 of 34 had altered suppression of DNA synthesis and 5 of 34 had altered suppression of IgG synthesis. Ratios of OKT4/T8 T cell subsets showed no difference between the study population, although 3 SLE family members had an increased ratio (greater than 2 SD) relative to controls. The 12 family members with either altered suppressor cell number or function had higher antibody levels to dRNA (Poly A . U) than did those with normal suppressor function and number. The results demonstrate that altered suppressor cell number and function occur in certain asymptomatic family members of SLE patients and may be weakly associated with markers of a preceding RNA viral infection.

Complement System Proteins↗
PubMed1982

An evaluation of commercial kits for the detection of antibodies to double-stranded DNA.

Antibodies to double-stranded (ds) DNA may provide useful information in the management of patients with systemic lupus erythematosus. commercial radioimmunoassay (RIA) kits for the detection of (ds) DNA antibodies (Lupo-Tec, Wampole Laboratories; anti-DNA kit, Amersham Corporation) were compared with a modified Farr assay and checked for intra-lot, inter-lot and inter-assay variation. Purity of DNA preparations was assessed using rabbit antibody to single-stranded (ss) DNA. Selected sera with low (less than or equal to 15%), moderately elevated (less than or equal to 40%), or markedly elevated (greater than or equal to 44%) (ds) DNA binding values (Farr assay) were tested. Positive and negative control sera when supplied with the kits also were evaluated. Normal sera were used as internal controls. A variable degree of intra-lot, inter-lot, and inter-assay correlation was observed. At low antibody levels, discordance was observed but values greater than or equal to 25% (Farr assay) were abnormally elevated in all kits tested. Clinical and laboratory personnel should be aware of potential pitfalls in RIA methods and carefully interpret results when commercial DNA kits are used.

Antibodies, Antinuclear↗