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Biomedical subjects

D I Bernstein

Publications and source records attributed to D I Bernstein.

At least 145 records · Page 8Linked to original sources
PubMed1990

Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants.

The safety, immunogenicity, and efficacy of WC3 rotavirus vaccine was evaluated in a double-blind, placebo-controlled trial of healthy infants 2-12 months of age; 103 received one dose of vaccine and 103 received placebo. Vaccination appeared to be safe and induced an antibody response (WC3 neutralizing antibody) in 97% of vaccinees. Only 9 (9%) of these, however, produced antibody to human rotavirus serotypes; at least 7 of the 9 were naturally infected before vaccination. Neither the number of symptomatic episodes of rotavirus diarrhea (21 vs 25) nor the number of moderate to severe rotavirus illnesses (9 vs. 15) was significantly different in vaccine or placebo recipients, respectively, during a predominantly serotype 1 rotavirus season. A slight but significant decrease in mean symptom score was detected in vaccine recipients. Despite an overall lack of efficacy, protection could be correlated to previous rotavirus infection, high levels of WC3 neutralizing antibody, and preexisting (maternal) serotype 1 neutralizing antibody with a titer greater than or equal to 30.

Antibodies, Viral↗
PubMed1990

Effect of vaccination on serotype-specific antibody responses in infants administered WC3 bovine rotavirus before or after a natural rotavirus infection.

In an evaluation of WC3 bovine rotavirus (serotype 6) vaccine in infants, some subjects experienced a natural serotype 1 rotavirus infection before vaccination and others after. Therefore, the effects of both WC3 and natural rotavirus strains as either primary or boosting immunogens on serotype-specific neutralizing antibody responses could be determined. After primary natural infection (symptomatic or asymptomatic), neutralizing antibody titers were highest to serotype 1 but were consistently high to serotype 3, and low titers (greater than or equal to 20) to serotypes 2 and 4 were often detected. Previous vaccination with WC3 had little effect on the magnitude of these responses. In contrast, subjects infected with serotype 1 strains before vaccination experienced large (average, 12-fold) rises in neutralizing antibody to human serotypes 1-4 when vaccinated with WC3. Thus, although WC3 and the natural strains are distinct serotypes, their epitopes were sufficiently similar that reinfection with WC3 could boost neutralizing antibody titers to human serotypes in subjects primed by a previous natural infection.

Antibodies, Viral↗
PubMed1990

Detection of asymptomatic initial herpes simplex virus (HSV) infections in animals immunized with subunit HSV glycoprotein vaccines.

The evaluation of herpes simplex virus (HSV) vaccine efficacy will require methods to detect asymptomatic acquisition of HSV infection and to assess the risk of recurrences in these patients. HSV-infected vaccinees should develop antibodies to HSV polypeptides not included in subunit vaccines. Sera from 57 HSV glycoprotein-vaccinated guinea pigs that had asymptomatic initial infections after genital HSV type 2 challenge were collected after vaccination but before HSV challenge and again 30 days after HSV challenge to determine the antibody response to HSV polypeptides. Antibodies to nonvaccine HSV polypeptides were detected in sera collected after viral challenge from 32 (56%) of these 57 animals. Twenty-six (81%) of the 32 animals with detectable antibody developed recurrent disease; however, recurrences also developed in 11 (44%) of the remaining 25 that did not show detectable antibody to nonvaccine HSV polypeptides. The magnitude of vaginal viral shedding during the initial disease period following challenge was significantly lower in animals that did not develop antibody to nonvaccine polypeptides compared with those that did develop antibody (area under the viral shedding curve, 5.2 +/- 3.2 versus 18.1 +/- 5.8; P less than 0.0001) . These data suggest that detection of antibody to nonvaccine HSV polypeptides will identify the majority (70%) of initially asymptomatic vaccinees that develop recurrent disease but that latency can be established even with markedly reduced levels of viral replication that did not induce a detectable antibody response.

Animals↗
PubMed1990

Serum-neutralizing antibody to VP4 and VP7 proteins in infants following vaccination with WC3 bovine rotavirus.

Serum specimens from infants 2 to 12 months old vaccinated with the WC3 bovine rotavirus were analyzed to determine the relative concentrations of neutralizing antibody to the VP4 and VP7 proteins of the vaccine virus. To do this, reassortant rotaviruses that contained the WC3 genome segment for only one of these two neutralization proteins were made. The segment for the other neutralization protein in these reassortants was from heterotypic rotaviruses that were serotypically distinct from WC3. Sera were examined from 31 infants who had no evidence of a previous rotavirus infection and the highest postvaccination WC3-neutralizing antibody titers (i.e., 160 to 600) of the 103 subjects administered the vaccine. A reassortant (3/17) that contained both neutralization proteins from the heterotypic rotaviruses, i.e., EDIM (EW strain of mouse rotavirus) VP7 and rhesus rotavirus VP4, was not neutralized by these sera (geometric mean titer [GMT], less than 20). A reassortant (E19) that contained EDIM VP7 and WC3 VP4 was also very poorly neutralized by these antisera (GMT = 20). In contrast, antibody titers to a reassortant (R20) that contained WC3 VP7 and rhesus rotavirus VP4 were higher than those against WC3 (GMTs of 458 and 313, respectively). Thus, VP7 appeared to be the dominant immunogen for production of neutralizing antibody after intestinal infection of previously uninfected infants vaccinated with WC3 bovine rotavirus.

Animals↗
PubMed1990

Evaluation of occupational asthma from airborne egg protein exposure in multiple settings.

We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.

Air Pollutants, Occupational↗
PubMed1989

Differential effect of amantadine hydrochloride on the systemic and local immune response to influenza A.

Anti-influenza serum and nasal antibody titers were followed during a double-blind, placebo-controlled, randomized study assessing the prophylactic efficacy of 50, 100, and 200 mg/day of amantadine hydrochloride against experimental challenge with influenza A/Beth/1/85. The geometric mean titers (GMT) of serum hemagglutination inhibition antibody (P = .05) as well as serum influenza-specific IgG (P = .004) were significantly lower for all amantadine groups when compared to placebo. There were no significant differences in the GMT of either type of serum antibody titer comparing any of the three amantadine groups. Viral titers were also lower in the amantadine groups compared to the placebo group and not significantly different among the three amantadine groups. Nasal antibody titers in the 100-mg and 200-mg amantadine groups were significantly lower than placebo titers (P = .002). Nasal antibody titers in the 50-mg amantadine group did not differ significantly from titers in the placebo group (P = .892). Possible reasons for the differential effect of amantadine on the serum and nasal antibody response are discussed.

Adolescent↗
PubMed1989

Induction and persistence of local rotavirus antibodies in relation to serum antibodies.

The induction and persistence of local rotavirus antibodies, including stool IgA, jejunal IgA, and jejunal neutralizing antibody, were evaluated in 14 adult volunteers infected with the CJN strain of human rotavirus. In addition, the relationships between local rotavirus IgA and serum rotavirus IgA, IgG, and neutralizing antibody were determined. Both stool and serum rotavirus IgA appeared to have similar kinetics. Both antibodies peaked by days 14-17 after inoculation in all subjects, then decreased rapidly. By days 26-28, titers had fallen to 13% and 30% of their respective peaks. Serum rotavirus IgG peaked somewhat later, occurring in five subjects on days 26-28. Serum neutralizing antibody peaked on days 26-28 in all but three subjects. Both serum IgG and neutralizing antibodies also declined more slowly than rotavirus IgA. Although all antibody concentrations had decreased to only a fraction of their peak responses by days 270-365 after rotavirus inoculation they remained higher than baseline levels. For example, stool rotavirus IgA concentrations were 13.5-fold higher than baseline, while jejunal rotavirus IgA and neutralizing antibody were 8.9- and 4.3-fold above baseline, respectively. Similarly, serum antibodies remained 3.7- to 11.2-fold higher than baseline at 270-365 days after rotavirus inoculation. These studies imply that serum rotavirus IgA is a good indicator of local antibody responses. Furthermore, although both serum and local antibody titers peaked within 2-4 weeks after infection, these antibodies persisted at above baseline concentrations for at least 9-12 months after infection.

Adolescent↗
PubMed1989

Clinical and immunologic studies of rapid venom immunotherapy in Hymenoptera-sensitive patients.

A 2- to 5-hour regimen of rapid venom immunotherapy (RVIT) was administered to 33 patients with anaphylactic sensitivity to Hymenoptera venom in a hospital setting in which full emergency resuscitation equipment was available. The RVIT was administered as 10 increasing doses of each treatment venom every 10 to 15 minutes to achieve a final dose on day 1 of 58.55 micrograms per venom. Patients returned for booster venom injections of 60 micrograms on day 3, 70 micrograms on day 7, 80 micrograms on day 21, and 100 micrograms on day 35 after RVIT. Serial antigen-induced leukocyte histamine release studies were performed on day 1 in 10 patients before and after RVIT, as well as 3 1/2 months after initiation of RVIT. Of 33 patients, 32 achieved a cumulative venom dose on day 1 of at least 50 micrograms, and the entire group received a mean dose of 95.46 micrograms. Local reactions during RVIT occurred in 18 (55%) patients. Four patients (12%) experienced mild systemic reactions during or after completion of RVIT. Subsequent booster venom doses administered to 29 patients were well tolerated. A decrease in venom-induced leukocyte-histamine release from baseline was detected in three (30%) patients immediately after RVIT and in seven (70%) patients months after achieving maintenance doses. Cutaneous sensitivity decreased by at least one log10 concentration in eight (32%) of 25 patients. Twenty-two natural re-sting events occurred in 12 (50%) of 24 patients surveyed after successful completion of RVIT, of whom seven identified the insect as one for which they had been treated. No systemic reactions were reported. Results of this study indicate that RVIT is a safe, alternative method of venom administration for patients who are at immediate risk for re-sting anaphylactic episodes.

Adult↗
PubMed1989

Progesterone-responsive urticaria and eosinophilia.

A 30-year-old black albino woman was first observed with a 4-year history of monthly urticarial episodes associated with hypereosinophilia. Hives consistently began at the end of menses and lasted for 1 to 2 weeks. A comprehensive evaluation excluded underlying malignancy and infection. There was no evidence of extracutaneous visceral involvement consistent with the primary hypereosinophilic syndrome. A 6-month prospective evaluation was performed, during which daily hive symptoms were recorded and weekly determinations of eosinophils, serum total IgE, progesterone, estradiol, and 24-hour urine histamine were obtained. Eosinophil counts (range, 4002 to 37,350 cells per cubic millimeter) increased in association with the onset of hives and decreased to baseline levels after their resolution. The 24-hour urine histamine peaked at the onset of each urticarial episode. When serum progesterone levels increased, the hives were quiescent and peripheral eosinophils decreased to baseline levels. Progesterone caused in vitro dose-related inhibition of antihuman IgE-induced histamine release from peripheral basophils of this patient. Treatment with oral medroxyprogesterone resulted in remission of urticaria and a decrease in eosinophil counts. This patient represents a unique case of chronic cyclic urticaria and hypereosinophilia that appears to be modulated by the effects of progesterone.

Adult↗
PubMed1989

Efficacy and safety of low dosage amantadine hydrochloride as prophylaxis for influenza A.

The efficacy and safety of prophylactic low dose amantadine hydrochloride was assessed in two double-blind, placebo-controlled, randomized studies. In a study of 476 subjects aged 18 to 55 years, adverse reactions were not significantly different between the group receiving 100 mg/day amantadine and the placebo group but significantly greater in the group given 200 mg/day (P less than 0.009). The influenza attack rate in this study was too low to assess efficacy. In an experimental challenge study of influenza A/Beth/1/85 in 78 subjects of similar age the prophylactic administration of 50 mg, 100 mg or 200 mg/day doses of amantadine were more effective than placebo in preventing influenza illness (P less than 0.02, 66, 74 and 82% protection, respectively), and in suppressing viral replication (P = 0.02). There was no significant difference between amantadine groups in influenza illness or viral shedding. Compared with the placebo group the 100 and 200 mg amantadine groups showed a significant decrease in infection rate (100 mg: 40% protection: P = 0.012; 200 mg: 32% protection: P = 0.045) whereas the 50 mg group did not (20% protection: P = 0.187). These results suggest that 100 mg/day of amantadine will reduce toxicity but maintain the prophylactic efficacy seen with 200 mg/day.

Adolescent↗
PubMed1989

Local and systemic antibody response to rotavirus WC3 vaccine in adult volunteers.

An evaluation of the safety and immunogenicity of WC3 rotavirus vaccine was evaluated in adult volunteers. Pre- and post-vaccination titers of neutralizing antibody to WC3 and to the four human rotavirus serotypes as well as serum and stool rotavirus IgA levels were measured. Vaccination was safe and did not induce elevation of liver enzymes. None of the 12 volunteers receiving WC3 vaccine shed detectable amounts of virus although antibody rises were detected in 11 of 12 vaccines. Nine developed and increase in WC3 neutralizing antibody, one additional subject had a rise in Wa (human serotype 1) neutralizing antibody while another subject only developed a rise in stool rotavirus IgA. All of the vaccine recipients with a rise in WC3 neutralizing antibody also developed a rise in neutralizing antibody against at least one of the four most common human rotavirus serotypes. A stool IgA rotavirus antibody response was detected in 6 of 9 WC3 recipients with measurable stool antibody. None of the control subjects developed significant rises in any of the antibody titers measured. WC3 rotavirus vaccine appears to be safe and induces systemic and local immune responses in adults suggesting that further evaluation of WC3 should be considered in infants.

Adult↗
PubMed1989

Golgi-like, transneuronal retrograde labelling with CNS injections of herpes simplex virus type 1.

The use of HSV1 as a retrograde transneuronal marker for the CNS was assessed in several neuroanatomical systems of the rat brain including the olfactory, visual and somatosensory systems. In all systems, retrograde transneuronal transport was observed; with appropriate survival times transport was evident in third and fourth order neurons in established neuronal circuits. A striking observation was the high frequency of neurons labelled in a Golgi-like manner. The visualization of even the finest dendritic processes provides information about the architecture of neurons several synapses removed from the site of injection. The Golgi-like labelling is so complete that it is possible to identify and process distal parts of dendrites for EM analysis. Thus, it should be feasible to identify synaptic inputs to the dendrites of neurons two or more synapses removed from the site of injection. There was spotty evidence for anterograde transport but the vast majority of the labelling could be accounted for by retrograde transport. With increased survival time, some regions, especially those located one synapse removed from the injection site, became necrotic and the virus spread to glia cells in addition to neurons in those regions. However, in regions more than one synapse removed from the injection there was negligible labelling of glial cells. Taken together, these results suggest that transneuronal retrograde labelling with HSV1 is a useful tool in the analysis of neural circuits.

Animals↗
PubMed1989

Effects of antibody to rotavirus on protection of adults challenged with a human rotavirus.

Effects of preinoculation rotavirus antibody titers on the probability of infection and illness were evaluated in adults challenged orally with different doses of a virulent human rotavirus (CJN strain). Preinoculation titers considered were serum neutralizing antibody, serum rotavirus IgA, serum rotavirus IgG, jejunal neutralizing antibody, jejunal rotavirus IgA, and stool rotavirus IgA. Doses of virus of either 9 x 10(1) or 9 x 10(3) focus-forming units were administered to 19 subjects each. Twenty-six were infected; 15 experienced illness. The probability of either outcome was unrelated to dose. Stool rotavirus IgA titers could not be correlated to either infection or illness, but the mean titers of the other five antibodies were significantly or nearly significantly lower in subjects infected or ill, when compared with those negative for either outcome. When analyzed by stepwise logistic regression, only serum rotavirus IgG remained significantly (P = .005) related to the probability of infection, and only jejunal neutralizing antibody remained significantly (P = .01) related to the probability of illness.

Adult↗
PubMed1989

Genital infections due to herpes simplex virus type 2 in male guinea pigs.

A small-animal model of genital herpes simplex virus (HSV) infection has not been available for investigating the pathogenesis of disease in males. Male Hartley guinea pigs were inoculated on the medial thigh with 10(5)-10(6) plaque-forming units of HSV type 2. Animals developed vesicular lesions in the genital area, including the penis. Transient urinary retention, hindlimb paralysis, and acute urethral shedding of HSV also occurred. During acute infection, virus was detected in neural and genital tissue homogenates, including the peripheral nerve, lumbosacral dorsal root ganglia (DRG), spinal cord, brain, vas deferens, epididymis, testes, seminal vesicle, and prostate. Recurrent disease developed in all animals. Persistent virus was detected in DRG but rarely in the vas deferens, seminal vesicle, epididymis, and testes. This model produces disease similar to that seen in men and should prove useful for studying the pathogenesis and immunology of male genital HSV type 2 infections.

Acute Disease↗
PubMed1989

Clinical and serological outcome of genital herpes simplex virus (HSV) type 2 inoculation following oral HSV type 1 infection in guinea-pigs.

The clinical and serological outcome of genital herpes simplex virus type 2 (HSV-2) inoculation in animals previously orally infected with HSV type 1 was evaluated. A prior HSV-1 oral infection modified the genital HSV-2 infection so that only four of 18 (22%) animals were initially symptomatic although all but one animal shed HSV-2 from the cervicovaginal area for at least 5 days following inoculation. Three of four animals with symptomatic initial disease also developed recurrences, as did an additional six animals that did not manifest acute genital disease. Anti-glycoprotein gG-1 antibody was found in 17 of 18 animals with only an HSV-1 infection and anti-gG-2 antibody in all of nine animals with only an HSV-2 infection. Anti-gG-2 antibody was detected in eight of 17 animals with a prior HSV-1 infection following HSV-2 inoculation and one had an indeterminate response. Eight of these nine animals developed recurrent genital disease compared to one of eight that did not respond to gG-2 (P less than 0.006). Thus a prior oral HSV-1 infection modified both the initial presentation of HSV-2 infection and the HSV type-specific serological response.

Animals↗
PubMed1989

Effects of the immunomodulating agent R837 on acute and latent herpes simplex virus type 2 infections.

R837 is an immune modulator with no in vitro activity against herpes simplex virus (HSV). We evaluated topical R837 as therapy for genital HSV type 2 infection using the guinea pig model of this disease. Furthermore, we investigated the effect of R837 therapy on acute and latent neural HSV infections. Therapy initiated 12 h after viral inoculation and given twice a day significantly reduced the acute neural infection so that HSV was recovered from only 1 of 64 neural tissue specimens obtained from R837 recipients compared with 43 of 56 specimens obtained from placebo recipients (P less than 0.0001). R837 initiated 36 h after HSV inoculation and given once a day also significantly reduced the total mean lesion score of the acute disease from 14.1 +/- 4.3 to 2.6 +/- 5.3 (P less than 0.0001) and shortened the period of vaginal HSV shedding from 6.9 +/- 1.7 to 3.2 +/- 1.4 days (P less than 0.001). R837-treated animals also developed fewer HSV recurrences than did controls (2.0 +/- 1.7 versus 5.1 +/- 1.7; P less than 0.0002). Latent HSV was detected in 23 of 24 dorsal root ganglia explant cultures from placebo recipients but in only 2 of 30 cultures from R837-treated animals, and HSV in these 2 cultures was detectable only with the addition of a demethylating agent. Topical R837 exhibited in vivo anti-HSV activity, reducing both acute and latent neural infections as well as acute and recurrent genital disease.

Adjuvants, Immunologic↗
PubMed1989

Prednisone pretreatment leads to histaminic airway hyporeactivity soon after resolution of the immediate allergic response.

We assessed the effect of prednisone pretreatment (50 mg/day for three days) on the development of the early increase in histamine reactivity that occurs soon after resolution of the immediate response in allergic humans. Four allergic subjects who were known to develop only isolated immediate responses upon Kentucky bluegrass inhalation, as well as four mild allergic asthmatic subjects known to develop typical dual phase responses, were evaluated. All testing was done more than nine weeks after the grass pollen season had ended. Allergen inhalation produced an immediate response in all subjects. However, upon resolution of the immediate response to allergen in these pretreated subjects, the PC200His in all dual responding asthmatics and in three of the four isolated immediate responders had substantially increased above baseline values. We conclude that prednisone pretreatment leads to histaminic hyporeactivity soon after resolution of the immediate allergic response in both dual responding asthmatics and isolated immediate responders. It would seem that this prednisone effect is independent of its potential influence on the influx of inflammatory cells into diseased airways.

Adult↗