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Biomedical subjects

D I Bernstein

Publications and source records attributed to D I Bernstein.

At least 181 records · Page 10Linked to original sources

Clinical and immunologic studies among egg-processing workers with occupational asthma.

Twenty-five workers in an egg-processing factory were evaluated for respiratory sensitization to inhaled egg proteins by a physician evaluation, serial peak expiratory flow rate (PEFR) measurements for a 1-week period, and immunologic tests. Immunologic studies included skin prick tests, serum-specific IgE (RAST), and specific IgG (ELISA) to solutions prepared from commercial food allergens: factory-powdered egg white and yolk products and purified egg white fractions, including ovalbumin, ovomucoid, lysozyme, and conalbumin. Six workers had significant daily PEFR lability (greater than 20%) of whom five had associated cutaneous reactivity to at least one egg allergen. A diagnosis of "definite asthma" was established in five workers suspected by the physician of having asthma. These five workers exhibited significant decrements in daily PEFR that were accompanied by bronchial symptoms. Occupational asthma was diagnosed by the physician in four of the five latter workers. Definite asthma was significantly associated with both cutaneous reactivity to egg allergens (p less than 0.01) and RAST binding (p less than 0.01). Of eight workers with cutaneous reactivity to at least one egg reagent, four workers (50%) were positive to only purified egg white fractions. The highest levels of RAST binding were detected in four workers, and the best binding activity was to ovomucoid and ovalbumin fractions. Elevated specific IgG responses were significantly higher in egg-factory workers to whole egg (p less than 0.005), lysozyme (p less than 0.002), and conalbumin (p less than 0.002) allergens compared to responses of nonexposed control subjects. However, no differences in specific IgG were detected between symptomatic and asymptomatic workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes.

The natural history of initial and subsequent recurrent herpes simplex virus (HSV) genital infection was studied in guinea pigs immunized with HSV glycoprotein vaccines before vaginal challenge with HSV-2. The vaccines used included HSV-1 glycoprotein B and HSV-1 glycoprotein D, both prepared by recombinant DNA techniques, and mixtures of HSV-1 or HSV-2 glycoproteins, prepared from infected cell monolayers by lectin chromatography. Immunizing guinea pigs with subunit HSV glycoprotein vaccines favorably altered the clinical and virological course of initial infection and substantially reduced the incidence, frequency, and duration of recurrent herpetic infections. The extent of protection was influenced by the nature of the glycoprotein vaccine, the immunizing dose, and the co-administration of adjuvant.

Animals↗

Antibody response to herpes simplex virus glycoprotein D: effects of acyclovir and relation to recurrence.

We developed an enzyme-linked immunosorbent assay (ELISA) for measuring the antibody response to herpes simplex virus (HSV) glycoprotein D (gD). The ELISA was specific and more sensitive than immunoblotting techniques. Antibody to HSV gD was detected in 10 of 12 sera (geometric mean titer, 36.3) obtained from HSV-2-infected guinea pigs 14 days after intravaginal inoculation, and the titer increased to greater than or equal to 5,120 on day 60. Therapy with acyclovir delayed and diminished the antibody response to gD, although by day 60 the titers of antibody to gD in acyclovir-treated animals were not significantly different from those in controls. An increased titer of antibody to gD seemed to be associated with a reduced number of recurrent episodes and to a reduced number of days with recurrent lesions.

Acyclovir↗

Oral ribavirin treatment of influenza A and B.

A loading dose and short-term administration of oral ribavirin significantly improved symptoms and signs of influenza type A or B infection in 25 patients. The antiviral effect was not significant. No adverse clinical effects or significant laboratory values were observed. Oral treatment of patients with influenza A or B infection might be possible with ribavirin.

Administration, Oral↗

Occupational asthma caused by himic anhydride.

Acid anhydride compounds are reactive chemicals that have been previously associated with immunoglobulin E (IgE) mediated occupational asthma. Twenty workers with exposure to himic anhydride powder used for the manufacture of a synthetic flame retardant were questioned about respiratory symptoms. The study was initiated after one individual from the plant developed asthma. A test for serum-specific IgE to human serum albumin conjugates of himic anhydride, phthalic anhydride, hexahydrophthalic anhydride and trimellitic anhydride was performed for seven workers with respiratory symptoms associated with himic anhydride exposure. Three of the seven symptomatic workers who reported wheezing at work exhibited elevated specific IgE to two or more acid anhydride-human serum albumin conjugates. Radioallergosorbent inhibition studies performed with sera containing high levels of himic anhydride-human serum albumin specific IgE from a symptomatic worker demonstrated cross-allergenicity between himic anhydride-human serum albumin and hexahydrophthalic anhydride-human serum albumin allergenic determinants. This study demonstrated that himic anhydride can elicit IgE-mediated sensitization in the workplace.

Adult↗

Rotavirus fecal IgA antibody response in adults challenged with human rotavirus.

Our studies of rotavirus challenge in adult volunteers enabled us to evaluate the relationship of pre-existing antirotavirus fecal IgA antibody to infection and illness and to investigate the local response to this infection. No relationship could be found between the pre-existing levels of fecal antirotavirus IgA antibody and protection from infection or illness. A greater than six-fold increase in the level of antibody was seen in 16/19 infected volunteers with determinable increases but in 0/15 controls who received less than the minimal infectious dose of rotavirus. Antibody levels increased rapidly in infected volunteers and were consistent with an anamnestic response. Two of seven volunteers who received an infectious dose of rotavirus but were considered uninfected on the basis of other laboratory methods had greater than or equal to six-fold increases of fecal antibody and one of these experienced symptoms compatible with a rotavirus infection. This finding indicates that an increase in fecal antibody may be a reliable indicator of rotavirus infection even in the absence of detectable shedding or seroconversion.

Adolescent↗

Delayed anaphylactoid reaction in a worker exposed to chromium.

A 29-year-old male welder reported systemic reactions after exposure to chromium. Inhalation challenge testing to 29 micrograms/m3 of sodium chromate aerosol resulted in late appearing systemic urticaria, angioedema, and severe bronchospasm that occurred at the same time as a threefold rise in plasma histamine. A direct leukocyte inhibitory factor test to 5.5 X 10(-6)mol/L Na2CrO4 was positive. Although the mechanism of this reaction is unknown, the positive leukocyte inhibitory factor and the general acceptance of hexavalent chromium as a contact skin sensitizer suggest that cell-mediated mechanisms could be involved.

Adult↗

Efficacy and safety of astemizole, a long-acting and nonsedating H1 antagonist for the treatment of chronic idiopathic urticaria.

The efficacy and safety of astemizole (AST), a new long-acting H1 antagonist with minimal sedative or anticholinergic side effects, were studied in an 8-week double-blind trial of 51 patients with chronic idiopathic urticaria. Patients with chronic idiopathic urticaria were randomized to AST-treated (10 mg every day) or placebo-treated groups. Patients were followed at weekly intervals and evaluated for pruritus, erythema, extent of wheals, frequency of urticarial episodes, and total control of urticaria. Only three of 27 AST-treated patients stopped the double-blind phase before 8 weeks because of inadequate response as compared to 11 of 24 placebo-treated subjects (p = 0.027). On the last evaluable visit of the double-blind phase of the study, 85% of the AST-treated patients reported an excellent or good response compared to 30% of the placebo-treated group (p = 0.0001). AST-treated patients also reported significant improvement compared to placebo-treated patients in pruritus (p = 0.0001), erythema (p = 0.0001), and extent of wheals (p = 0.003). Mild sedative effects were observed in only two of 27 patients receiving AST. It was concluded that AST is a potent and safe drug for symptomatic control of chronic idiopathic urticaria.

Adult↗

Evaluation of the herpes simplex virus antiviral activity of pyrethrins.

Pyrethrins, complex esters extracted from Chrysanthemum cinerariaefolium, exhibit only minimal in vitro activity against herpes simplex virus (HSV). Employing a guinea pig model of HSV genital infection, no in vivo activity could be demonstrated. Although purported to be an effective remedy for the treatment of genital herpes, we were unable to demonstrate efficacy for either the oral administration of an alcoholic solution of pyrethrins or the topical application of pyrethrins in mineral oil.

Administration, Oral↗

Genital reinfection after recovery from initial genital infection with herpes simplex virus type 2 in guinea pigs.

The natural history of genital reinfection with herpes simplex virus type 2 (HSV-2) three weeks to one year after initial infection was explored by using a guinea pig model. Intravaginal reinoculation with HSV-2 of animals that had recovered from initial genital infection produced by wild-type or thymidine kinase-deficient HSV-2 produced asymptomatic genital reinfection characterized by high-titered replication of HSV-2 in the vaginal vault. Reinoculation did not result in acute neural infection, as was seen during initial genital herpes, and no evidence of latent infection by the rechallenge strain could be demonstrated. The frequency of recurrences appeared to be established by the initial infection because reinfection did not alter the pattern of recurrent genital herpes. The present study suggest that asymptomatic reinfection may produce a reservoir of communicable virus and that initial infection with a less virulent mutant of HSV-2 may provide protection against subsequent reexposure to wild-type HSV-2.

Animals↗

Human rotavirus studies in volunteers: determination of infectious dose and serological response to infection.

An unpassaged, safety-tested strain (CJN) of human rotavirus from a stool specimen of a hospitalized child was administered orally to 62 adult volunteers for determination of the dose required to produce infection with or without illness. Subjects ingested doses ranging from 9 X 10(-3) to 9 X 10(4) focus-forming units in buffered salt solution after consumption of 50 ml of 4% NaHCO3. The amount of virus in the inoculum required to cause infection (shedding of virus, seroconversion, or both) in study subjects was comparable to the minimum detectable in cultures of primary monkey kidney cells. Seventeen of 30 infected subjects became ill with doses equivalent to that required for infection. Although the preinoculation titers of serum neutralizing antibody to the challenge virus in study subjects ranged from less than 1:2 to 1:1,600, the concentration of serum antibody could not be correlated with protection from infection or illness in subjects given an infectious dose of virus.

Adult↗

Antibody response, recurrence patterns and subsequent herpes simplex virus type 2 (HSV-2) re-infection following initial HSV-2 infection of guinea-pigs: effects of acyclovir.

The production of antibody to specific herpes simplex virus type 2 (HSV-2) polypeptides, the recurrence patterns and the susceptibility to re-infection were studied in the guinea-pig model of genital HSV-2 infection. Further, we defined the effects of acyclovir (ACV) therapy on these parameters of infection. Treatment with ACV reduced the clinical severity of the initial disease but did not affect vaginal viral shedding. Production of neutralizing antibody as well as antibody to the nucleocapsid protein, and glycoproteins B, D and G were all delayed in ACV recipients. ACV treatment of initial infection did not significantly alter the pattern of subsequent recurrence although by several criteria treated animals tended towards decreased recurrences. Re-inoculation with a second strain of HSV-2 resulted in a local cervicovaginal infection but, except for one ACV-treated animal, neural tissue was protected from re-infection.

Acyclovir↗

Zosteriform spread of herpes simplex virus type 2 genital infection in the guinea-pig.

A model of herpes simplex virus type 2 (HSV-2) infection was developed in the guinea-pig that permits investigation of the role of neural spread of virus in the pathogenesis of genital skin disease. After HSV-2 inoculation of an abraded area lateral to the external genital skin, virus was first detected in the ipsilateral (to the inoculation site) peripheral nerves or genital skin on day 2 or 3 post-inoculation followed by detection in the ipsilateral dorsal root ganglia and spinal cord on day 3 or 4. Virus also spread to the contralateral dorsal root ganglia, contralateral peripheral nerves and contralateral genital skin on day 4 or 5 although lesions were only rarely detected on the contralateral side. Genital skin lesions first developed on day 5 and were followed by the development of lesions along the medial aspect of the ipsilateral hindlimb. Virus was first detected in the vaginal vault on day 4 or 5. The development of lesions appeared to be unrelated to vaginal virus replication but was associated with the recovery of virus from peripheral nerves. Recurrent genital skin lesions were seen more commonly on the inoculated side than the contralateral side. Since the development of skin lesions appeared to result from virus emerging from nerve endings, an event similar to the terminal event that is believed to be involved in the development of recurrent lesions, we now have a model which may be useful in further exploring the pathogenesis of herpetic disease.

Animals↗

Comparison of Western Blot Analysis to microneutralization for the detection of type-specific herpes simplex virus antibodies.

A newly developed system (as described in the previous paper) employing separated herpes simplex virus (HSV) polypeptides electrophoretically transferred to nitrocellulose paper, Western Blot Analysis (WBA), was compared to microneutralization (MN) for the detection of type-specific antibody to HSV types 1 and 2 in 98 human sera. Sera containing HSV1-specific antibodies reacted at least twofold more densely (as quantitated by densitometric scanning) to HSV1 than HSV2 polypeptides, while sera with HSV2-specific antibodies reacted twofold more densely to HSV2 polypeptides. The reliability of this system was determined (1) by analysis of sera from patients with true primary herpes simplex infections, (2) by adsorption studies that removed cross-reacting antibodies, and (3) by comparison with neutralization. Of 36 sera found to have HSV1-type-specific antibody by WBA, 83% had MN ratios of less than 85 (indicating HSV1 antibody), while of 28 sera found to have HSV2-type-specific antibody by WBA, 89% had MN ratios of greater than 85 (indicating HSV2 antibodies). The MN ratio obtained on sera felt to have both HSV1-type-specific and HSV2-type-specific antibody by WBA ranged from 67 to 160. WBA agreed more closely with clinical isolates and adsorption studies than MN. This system not only accurately determines the HSV-type-specific antibody status of patients but provides important information on the specific immunogenic proteins.

Antibodies, Viral↗

Antibody response to type-common and type-unique epitopes of herpes simplex virus polypeptides.

Herpes simplex virus type 1 (HSV1) and type 2 (HSV2) polypeptides with type-common and type-unique epitopes were identified using cross-adsorbed hyperimmune rabbit sera and Western blotting techniques. Twelve HSV1 and fourteen HSV2 polypeptides with type-specific epitopes were identified. Cross-adsorbed human sera reacted to a subset of the type-specific epitopes defined by rabbit sera. Human sera with both HSV1- and HSV2-specific antibodies were identified by their reaction to HSV1-type-specific epitopes after adsorption with HSV2, and HSV2-type-specific epitopes after adsorption with HSV1. Mixing experiments demonstrated the sensitivity of this assay for detecting HSV2-type-specific antibody in the presence of HSV1 antibody. This technique has proven useful in the study of immune response to individual HSV polypeptides during human HSV infections, while the presence of these type-unique epitopes on HSV polypeptides allows for the detection of type-specific antibodies in human sera.

Antibodies, Viral↗

Detection of IgE-mediated respiratory sensitization in workers exposed to hexahydrophthalic anhydride.

Twenty-seven workers with occupational exposure to hexahydrophthalic anhydride (HHPA) from an epoxy resin molding system were studied to evaluate the nature of their reported respiratory complaints. The workers were evaluated by questionnaire, pulmonary function tests, and serologic investigations. The presence of serum-specific IgE and IgG to an HHPA-human serum albumin (HSA) conjugate was measured by use of RAST and ELISA assays. Estimates of exposure to HHPA were made for each worker on the basis of job description and environmental sampling. Seven workers reported symptoms of asthma and rhinitis; four workers had symptoms consistent with occupational asthma. Fourteen of the remaining 20 workers reported nasal or ocular symptoms while they were at work. No worker demonstrated a significant (greater than 20%) pre-to postshift decrement in FEV1. Twelve workers had significant levels of specific IgE to HHPA-HSA; 11 had elevated levels of specific IgG to HHPA-HSA. A group of workers estimated to have higher exposures to HHPA had a significantly higher mean total IgE level (p less than 0.05) and significant titers of HHPA-HSA-specific IgE or IgG, or both (p = 0.048) as compared to a group with lower exposure to the anhydride. All four workers with occupational asthma/rhinitis had significant levels of specific IgE to HHPA-HSA (ranging from 8.7% to 23.4% RAST binding); three workers did not work directly in the HHPA area but were located in nearby sections of the plant with lower exposures to HHPA. Three workers with symptoms of asthma not clearly associated with the workplace did not have significantly elevated specific IgE levels. Another radioimmunoassay with the use of beads coated with mouse monoclonal antihuman IgE was used to quantitate the amount of specific anti-HHPA-HSA binding (range 1.0 ng to 32.6 ng/ml) present in workers' sera. The solid-phase bead radioimmunoassay was inhibited by the homologous HHPA-HSA conjugate but not by HHPA hapten alone in two workers, suggesting that these workers were sensitized to new antigenic determinants. We conclude that HHPA is a potent industrial sensitizer and is capable of inducing IgE-mediated disease. Prospective investigations are required to define the incidence and severity of clinical sensitivity.

Antibody Specificity↗

Prospective evaluation of chymopapain sensitivity in patients undergoing chemonucleolysis.

Immediate anaphylactic reactions after intradiscal chymopapain (CP) injection may occur in 1% of patients undergoing chemonucleolysis (CN). Skin prick testing to CP (10 mg/ml), a prescreening history, and CP serum-specific IgE determinations by the RAST method were performed in order to identify patients presensitized to CP before CN. Follow-up repeat CP skin testing and serum-specific IgE were done 2 to 6 weeks after CN to detect CP IgE-mediated sensitization resulting from the injection. Three of 84 patients who exhibited positive skin tests to CP before CN did not receive CP injections. Only one of the three patients (33%) was detected with elevated CP serum-specific IgE before CN. No immediate severe anaphylactic reactions caused by CP injection were encountered in the remaining 81 patients with negative CP skin tests and RASTs before CN. Eight (10%) nonlife-threatening immediate and late reactions were associated with conversion from negative skin tests and RASTs before CN to positive skin tests or RASTs after CN. Overall, 19 of 52 (37%) patients who returned for follow-up testing developed cutaneous sensitization to CP after CN. Despite the fact that RAST values after CN in these patients were significantly higher (p less than 0.002) than those with negative skin tests after CN, the sensitivity of the RAST was only 72% for identifying patients who developed positive CP skin tests after CN. This study demonstrated that CP skin testing is essential for prescreening patients because it was more sensitive than RAST for identification of CP sensitivity both before and after CN. Late allergic reactions and cutaneous sensitization to CP were common sequelae of CN.

Anaphylaxis↗