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Biomedical subjects

D I Bernstein

Publications and source records attributed to D I Bernstein.

At least 163 records · Page 9Linked to original sources
PubMed1988

Antibody to cloned HSV glycoproteins B and D plus adult human leukocytes protect neonatal mice from lethal HSV infection.

Antisera produced by HSV infection or following vaccination of guinea pigs with the cloned herpes simplex virus (HSV) glycoproteins gB and gD were compared for in vitro antibody-dependent cellular cytotoxicity (ADCC) activity and for in vivo protection. Antibody from guinea pigs was able to participate in ADCC with human mononuclear cells in vitro, anti-gBgD serum being equivalent to HSV convalescent sera. In vivo, each of the guinea pig sera was able to protect neonatal mice from a fatal HSV-1 infection when given with human mononuclear cells but not when given alone. The anti-gBgD serum was the most effective in vivo, protecting 15 of 17 (88%) neonatal mice when given at a 10(-4) dilution with human mononuclear cells and was the only guinea pig serum protective at a 10(-6) dilution (5 of 7 neonatal mice).

Animals↗
PubMed1988

Modification of immunological responses and clinical disease during topical R-837 treatment of genital HSV-2 infection.

R-837, a compound with no in vitro anti-HSV activity, was administered intravaginally to guinea pigs (5 mg/kg every 12 h) for five days beginning 12 h after genital HSV-2 inoculation. Drug treatment reduced vaginal viral replication (P less than 0.0001), completely protected against primary disease and reduced recurrent genital HSV disease (P less than 0.0001). Drug treatment also induced mild fever, weight loss, and decreased water intake. R-837 was a potent interferon inducer, which also induced variable enhancement of cell-mediated cytolytic activity against HSV-2 targets. Less than 36 h of vaginal HSV shedding was observed in animals with R-837 induced early enhancement of HSV-target cytolysis. Compared to placebo, R-837 decreased ELISA and ADCC antibody to HSV-2, but accelerated HSV-2 specific in vitro IL-2 production and peripheral blood mononuclear cell (PBMC) proliferation. R-837 exhibited potent anti-HSV activity in vivo apparently due to cytokine induction and enhancement of cell-mediated responses.

Administration, Intravaginal↗
PubMed1988

Enhanced in vitro reactivation of latent herpes simplex virus from neural and peripheral tissues with hexamethylenebisacetamide.

We evaluated the effect of the demethylating agent hexamethylenebisacetamide on reactivation of latent herpes simplex virus type 2 (HSV-2) from guinea pig neural and extraneural tissues. Four explant cultures from the dorsal root ganglia of 42 latently infected guinea pigs and vaginal and cervical explant cultures from 33 animals were divided so that half received 5 mM of hexamethylenebisacetamide supplemented media and half media alone. HSV-2 was recovered earlier and from a greater percentage of treated cultures than controls. For example, seven days after explant, HSV-2 was recovered from 35 of 84 (42%) treated dorsal root ganglia cultures compared to seven of 84 control cultures (p less than 0.0001). Likewise, HSV-2 was recovered seven days after explant from 11 of 66 (17%) treated external genital skin cultures and 2 of 66 control cultures (p less than 0.009), Hexamethylenebisacetamide had no effect on productive HSV-2 infection in guinea pig dorsal root ganglia cultures. This study provides evidence for a role of demethylation in the reactivation of latent HSV from neural as well as peripheral tissues and suggests that latent virus exists at these sites in a similar state. Hexamethylenebisacetamide should be useful in studies of herpes virus latency because it decreases the time necessary to recover virus from latently infected tissues and enhances the recovery of virus.

Acetamides↗
PubMed1988

Immune responses of cynomolgus monkeys to phthalic anhydride.

Four groups of four Macaca fascicularis monkeys were administered 10 consecutive weekly subcutaneous injections of 2 mg aluminum hydroxide plus one of the following: 200 micrograms of phthalic anhydride (PA)-monkey serum albumin (PA-MSA, group 1); 200 micrograms of PA dissolved in ethanol-saline (EtOH-sal, group 2); 200 micrograms of MSA (group 3); or EtOH-sal alone (group 4). Direct intracutaneous tests to PA-MSA, PA-EtOH-sal, MSA, and EtOH-sal were applied at biweekly intervals throughout the course of the immunization. Serum-specific IgG to PA-MSA and specific IgE to PA-MSA were determined at 2-week intervals according to the ELISA and RAST methods, respectively. The prevalence of cutaneous sensitivity to PA-MSA in the PA-MSA-immunized group (group 1) was significantly greater after 4 and 6 (p less than 0.01) and 8 and 10 (p less than 0.05) weeks, compared with the other treatment groups. Significantly elevated (p less than 0.01) PA-MSA-specific IgG was also observed in monkeys in group 1 compared with the other treatment groups. No significant changes in PA-MSA RAST or total IgE were observed in any group during the study. These results indicate that parenteral sensitization to PA in subhuman primates requires the presence of new antigenic determinants formed by PA on protein carriers.

Animals↗
PubMed1988

Pulmonary and immunologic evaluation of foundry workers exposed to methylene diphenyldiisocyanate (MDI).

A cross-sectional evaluation was performed of workers in a steel foundry in which methylene diphenyldiisocyanate (MDI) was used as a component of a binder system used to make cores and molds. Preshift and postshift spirometry and clinical evaluations were performed on 26 currently exposed (group I), on six formerly exposed (group II), and on 14 nonexposed workers to MDI (group III). Serum samples were assayed for total antibody binding, specific IgG by ELISA, and specific IgE by the RAST method to MDI-human serum albumin (HSA). Symptoms compatible with occupational asthma were elicited from seven (27%) of 26 group I workers and from three of six group II workers. No symptoms were reported by group III workers. Intrashift change in FEV1 (a mean decrease of 0.049 L) in group I workers was significantly decreased compared to that in unexposed group III workers (a mean increase of 65 ml; p = 0.043). Specific IgG and total antibody responses to MDI-HSA were detected only in workers with current or former exposure to MDI. Only one worker was identified with IgE-mediated occupational asthma exhibiting a positive prick test and elevated RAST to MDI-HSA of 25.5% bound. In this occupational setting, polyclonal immune responses to MDI-HSA and clinical sensitization to MDI were demonstrated to occur.

Adult↗
PubMed1988

An open study of auranofin in the treatment of steroid-dependent asthma.

To determine the efficacy of oral gold in asthma, 20 patients with steroid-dependent asthma received auranofin at a dose of 3 mg by mouth, twice daily, in a 24-week open clinical trial. Prospective evaluation of bronchial responsiveness to methacholine was determined before and 8 and 16 weeks after initiation of auranofin therapy. Serial spirometry (FEV1 and FVC), lung volumes, and diffusing capacities (single breath carbon monoxide diffusing capacity of the lungs) were measured before and at 10 and 20 weeks after treatment. All subjects were required to record concomitant medications, symptom scores, and morning and evening peak expiratory flow rates. In vitro immunologic studies performed before and after 8 and 20 weeks of auranofin therapy included leukocyte histamine release in response to antihuman IgE, lymphocyte blast transformation in response to concanavalin A and phytohemagglutinin, and leukocyte inhibitory factor activity in response to Candida albicans and tetanus toxoid antigens. In 18 patients evaluated, there were no significant differences between baseline and posttreatment spirometry, single breath carbon monoxide diffusing capacity of the lungs, and lung volumes. At week 16 of treatment, the steroid cumulative dose or the total prednisone dose administered from 7 days before through 10 days after each methacholine test day decreased from a mean of 293 +/- 125 mg at baseline to 192 +/- 115 mg. At week 16, nine of 18 patients (50%) exhibited decreased methacholine responsiveness as defined by a more than one-half log10 increase in the concentration of methacholine causing a 20% decrease in FEV1. A significant correlation (r = 0.60) was observed between the increase in the concentration of methacholine causing a 20% decrease in FEV1 and the decrease in steroid cumulative dose after 16 weeks of treatment. Leukocyte histamine release to anti-IgE exhibited significant reductions from baseline at week 20 to 10(-2) (p less than 0.002) and at 10(-3) (p less than 0.005) dilutions. At week 20, leukocyte inhibitory factor activity in response to Candida increased from baseline at the 0.1 mg per well (p = 0.025) and 1 mg per well (p = 0.05) concentrations; similarly, the responses to tetanus toxoid increased at the 1 mg per well (p less than 0.05) and 0.1 mg per well (p less than 0.01) concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Herpes simplex virus glycoprotein treatment of recurrent genital herpes reduces cervicovaginal virus shedding in guinea pigs.

Treatment of previously infected guinea pigs with herpes simplex virus (HSV) glycoproteins reduces the frequency and severity of subsequent genital recurrences. An effective vaccine should also reduce episodes of viral shedding. In this study, HSV glycoproteins B and D treatment of animals experiencing recurrent genital herpes reduced the frequency of both clinical recurrences and cervicovaginal viral shedding. When virus was shed, however, the peak viral titer and duration of shedding was unaltered.

Animals↗
PubMed1988

Antibody to herpes simplex virus (HSV) ICP-35 proteins after HSV challenge of animals immunized with HSV subunit vaccines.

The serological response to the ICP-35 group of herpes simplex virus type 2 (HSV-2) proteins was examined 30 d after vaginal challenge with HSV-2 of guinea pigs previously immunized with HSV glycoproteins. Detection of antibodies to ICP-35 proteins correlated best with the magnitude of vaginal viral replication. Animals that developed antibody to ICP-35 proteins had more-frequent recurrences (P less than .0002) that were of longer duration (P less than .005) than animals that did not. By covariate analysis the number of recurrences appeared to be related to the severity of the acute disease, inversely related to the enzyme-linked immunosorbent assay titer of antibody to HSV glycoproteins, and related to the detection of antibody to ICP-35 proteins. The duration of recurrent disease, however, could only be correlated with the presence of antibody to ICP-35 proteins. Detection of antibody to ICP-35 proteins is thus a useful prognostic indicator for identifying animals that developed more-severe recurrent disease.

Acute Disease↗
PubMed1988

Enhanced in vitro reactivation of herpes simplex virus type 2 from latently infected guinea-pig neural tissues by 5-azacytidine.

5-Azacytidine (5-AZC) reduces cytosine methylation in DNA and has been reported to activate quiescent virus genes. Treatment of explant cultures of latently herpes simplex virus type 2 (HSV-2)-infected guinea-pig dorsal root ganglia and spinal cords in vitro with 5-AZC significantly enhanced the rate of HSV recovery. Both the number of isolates from ganglia (P less than 0.001) and the rate of recovery (P less than 0.001) were significantly increased with the addition of 50 microM-5-AZC to explant cultures. Increased virus recovery appeared to be due to the induction of reactivation of latent virus, rather than an increase in replication, since 5-AZC inhibited HSV replication. These data support a role for methylation in HSV latency and reactivation.

Animals↗
PubMed1988

Ribavirin small-particle-aerosol treatment of influenza B virus infection.

In a randomized double-blind trial of aerosolized ribavirin for the treatment of influenza B virus infection, no significant difference was found in the febrile course or symptom score of the ribavirin-treated versus placebo-treated patients. The apparent lack of efficacy in this study as compared with that in previous studies is unexplained.

Adult↗
PubMed1988

Double-blind comparison of terfenadine, chlorpheniramine, and placebo in the treatment of chronic idiopathic urticaria.

The efficacy of terfenadine, a nonsedating H1 antihistamine, in the management of chronic idiopathic urticaria was compared with chlorpheniramine and placebo in a parallel multicenter trial. Subjects with symptoms of hives for 3 days per week for at least 6 weeks were initially screened and admitted if no identifiable cause for symptoms could be determined. Patients entered a single-blind placebo period, and if hives of moderate severity were present for at least 3 days during the week, they were randomly assigned in a double-blind fashion to take terfenadine, 60 mg twice daily, chlorpheniramine, 4 mg three times a day, or placebo for 6 weeks. Data were analyzed for 122 patients. Those patients receiving both active treatments noted significant improvement in symptoms: pruritus, redness, number of hives, and waking hours during which hives were present, at the end of the first day of therapy. Symptom control by terfenadine was statistically superior to placebo during all 6 weeks, as rated by both patients and investigators. However, statistical significance was not achieved for chlorpheniramine at all observation points. Diphenhydramine was permitted as a relief medication for refractory symptoms and was taken by 52% of subjects receiving placebo, 26% taking chlorpheniramine, and only 9% of patients who were receiving terfenadine. In addition to providing superior symptom control, terfenadine caused less drowsiness and fatigue than chlorpheniramine. Terfenadine is a useful therapeutic agent for primary management of chronic idiopathic urticaria.

Adolescent↗
PubMed1987

Occupational asthma from inhaled egg protein.

We evaluated workers and performed an industrial hygiene assessment at a plant where raw eggs are processed into powdered egg yolk and whole egg. Egg dust levels in the packaging room straddled the American Conference of Governmental Industrial Hygienists' (ACGIH) exposure guideline of 10 mg/m3 for nuisance dust. We obtained medical histories from 25 workers, and performed physical examinations, spirometry, and serial determinations of peak expiratory flow rate (PEFR) by portable meter every 3 hrs (while awake) for 7 days. We defined symptomatic bronchial lability to be a decrement in PEFR on any one day of 20% or more of the day's maximum, with concurrent symptoms. Skin-prick tests and serum assays for specific IgE by the radioallergosorbent (RAST) method were performed to assess sensitivity to commercial egg proteins, egg protein fractions, and freshly prepared extracts of whole egg powder and yolk. We classified participants as definite cases of asthma if both the examining physician diagnosed asthma and symptomatic bronchial lability was demonstrated by serial PEFR determinations. Definite noncases of asthma were those participants in whom the physician did not diagnose asthma and in whom symptomatic bronchial lability was not demonstrated by PEFR. All five definite cases, compared to three of 16 definite noncases of asthma, had one or more positive skin-prick tests to egg proteins. Four of five cases, compared to 0 of 14 noncases, who had serum determinations, had an elevated RAST to one or more of the egg proteins. This study demonstrates that occupational asthma associated with IgE-mediated allergy to egg proteins occurs among workers exposed to inhaled egg proteins.

Air Pollutants, Occupational↗
PubMed1987

Cockroach sensitization in laboratory workers.

Six laboratory workers who were exposed to American cockroaches (AC) and German cockroaches (GC) while they were performing immunologic experiments were evaluated for cockroach hypersensitivity. Prick skin testing and RAST were performed with whole body extracts (1:20 wt/vol) of AC, brown-banded (BB), and GC species as well as hemolymph and fecal (F) extracts of AC. Three of six workers reported work-related nasal and ocular symptoms associated with xenografting and bleeding of cockroaches. All three symptomatic workers exhibited cutaneous reactivity to at least one cockroach antigen. Elevated RAST binding was observed in one of the three symptomatic workers. A nasal provocation to AC was positive in the most symptomatic worker at a provocative dose of 3.2 X 10(-3) mg causing a 50% decrease of nasal flow rate from baseline. After pretreatment with nasal cromolyn, the provocative dose causing a 50% decrease from baseline increased to 2.6 X 10(-1) mg. Nasal provocation with the same concentrations of AC were negative in two skin test negative subjects. RAST-inhibition studies demonstrated cross inhibition of the serum-specific IgE binding to AC-hemolymph by AC, GC, and BB whole body extracts. However, specific IgE binding to AC-F was inhibited by AC-F and AC but not by GC or BB whole body extracts, suggesting there was greater specificity of the F allergens. This study demonstrated that cockroach allergens elicit IgE-dependent upper respiratory sensitization in the workplace.

Adult↗