Search PubMed⌕ Search

Biomedical subjects

S A Plotkin

Publications and source records attributed to S A Plotkin.

At least 127 records · Page 7Linked to original sources

Immune response of infants and children to low-passage bovine rotavirus (strain WC3).

A bovine rotavirus (strain WC3) was isolated from a calf in Pennsylvania and adapted to growth in continuous Cercopithecus cell line CV1. A pool for human vaccine trials was produced at the 12th cell culture passage level. After preliminary testing in adults and older children, a dose of 3 X 10(7) plaque-forming units was given by mouth to 52 infants and children aged 5 months to 6 years. No clinical sequelae were detected, and shedding in feces was detected in only 30% of tested infants. A serum-neutralizing antibody response was induced in 95% of 21 infants aged 5 to 11 months; response rates were slightly reduced in older infants. The antibody response was primarily directed toward bovine rotavirus, but a response to human serotype 3 rotavirus was also observed in approximately 50% of vaccinees. After vaccination with WC3, infants with preexisting antibody to rotaviruses of human serotype 1 or 3 frequently exhibited a booster response to those serotypes. WC3 is a candidate rotaviral vaccine deserving larger trials in children.

Adult↗

A rapid microneutralization assay for cytomegalovirus.

A rapid, simple and reproducible microneutralization test for human cytomegalovirus is described. The results can be read in 1-2 days and the neutralization titer detected in human and guinea pig sera and in monoclonal antibody-containing supernatants is consistent with that derived by the plaque-reduction neutralization test.

Animals↗

Response of adult human volunteers to oral administration of bovine and bovine/human reassortant rotaviruses.

Small groups of adult volunteers, in sequence, were inoculated orally with inactivated purified bovine rotavirus of strain NCDV, with live NCDV purified or unpurified and with two different NCDV X human rotavirus reassortant viruses. One of five volunteers given 200 micrograms of ultravioletinactivated NCDV developed a virus-neutralizing (VN) and a binding antibody response detected by enzyme-linked immunosorbent assay (ELISA). Four of 10 volunteers given from 1 X 10(6) to 1 X 10(8) p.f.u. of live NCDV developed VN antibody, but nine of 10 responded when ELISA, HAI and radioimmuno-precipitation tests for serum antibody were also considered. Two different NCDV X human serotype 1 Wa strain virus reassortants, each containing Wa gene segment 9 and the serotype 1 neutralization phenotype, were administered orally in doses up to 10(6) p.f.u. The reassortants were relatively ineffective in eliciting a serum antibody response at the dosage level employed.

Administration, Oral↗

A practical guide to the diagnosis of congenital infections in the newborn infant.

Every attempt should be made to identify an etiologic agent in infants with suspected congenital infection. Some of the infections are treatable, such as herpes simplex, syphilis, and toxoplasmosis. For other infectious agents (i.e., CMV and rubella), close follow-up will enable early detection of hearing impairment and permit early educational intervention. In addition, appropriate isolation measures will reduce the risk of nosocomial infections due to herpes simplex, rubella, hepatitis B, and CMV. Rational use of the available diagnostic tools will enable detection of most symptomatic congenitally infected neonates at a reasonable cost.

Antibodies↗

Differentiation of TERA-2 human embryonal carcinoma cells into neurons and HCMV permissive cells. Induction by agents other than retinoic acid.

Retinoic acid induces the differentiation of NTERA-2 cl. D1 human embryonal carcinoma (EC) cells into neurons, cells permissive for the replication of human cytomegalovirus (HCMV), and other cell types that cannot as yet be classified but are distinguishable from the stem cells. We tested several additional agents for their ability to induce the differentiation of these EC cells. No differentiation was induced by butyrate, cyclic AMP, cytosine arabinoside, the tumor promoter 12-0-tetradecanoylphorbol 13-acetate (TPA), or the chemotherapeutic agent cis-diaminedichloroplatinum, although morphological changes were detected at the highest concentrations of these agents that permitted cell survival. However, retinal, retinol, 5-bromouracil 2'deoxyribose (BUdR), 5-iodouracil 2'deoxyribose (IUdR), hexamethylene bisacetamide (HMBA), dimethylacetamide (DMA), and dimethylsulfoxide (DMSO) all induced some neuronal differentiation, but to a lesser extent than retinoic acid. Also, BUdR, IUdR, HMBA, and DMA induced the appearance of many cells permissive for the replication of HCMV. Differentiation was, in all cases, accompanied by the loss of SSEA-3, a globoseries glycolipid antigen characteristically expressed by human EC cells. However, another glycolipid antigen, A2B5, which appears in 60%-80% of differentiated cells 7 days following retinoic acid induction, was detected in less than 20% of the cells induced by the other agents studied. This implies that the HCMV-permissive cells induced by retinoic acid are not identical to those induced by BUdR, IUdR, and DMA.

Acetamides↗

Immune-specific gamma interferon production correlates with lymphocyte blastogenesis.

Gamma interferon (IFN-gamma) production, measured by a new commercially available radioimmunoassay, and lymphocyte blastogenesis were investigated in human peripheral lymphocyte cultures from healthy adults stimulated by crude cytomegalovirus (CMV) antigen. Mononuclear cells were obtained from 32 healthy adults (18 CMV seropositive [S+] and 14 CMV seronegative [S-]) by Ficoll-Hypaque gradients and cultured in microtiter plates containing CMV antigen. Lymphocyte blastogenesis ([3H]thymidine uptake) and IFN-gamma were determined on day 6. The mean stimulation index for S+ individuals was significantly greater than that for S- individuals (P less than 0.001). Similarly, the IFN-gamma stimulation index was greater for S+ individuals than for S- individuals (P less than 0.005). A significant increase in the concentration of IFN-gamma (10 NIH units/ml) was observed for S+ individuals at 24 h of antigen stimulation, with peak levels at 4 days. The radioimmunoassay for IFN-gamma production by antigen-stimulated lymphocytes in vitro (IMRX; Centocor Inc., Malvern, Pa.) is a rapid and sensitive measure of cell-mediated immunity.

Adult↗

Immune responses to isolated human cytomegalovirus envelope proteins.

A group of envelope proteins of human cytomegalovirus, gA protein (L. Pereira, M. Hoffman, M. Tatsuno, and D. Dondero, Virology 139:73-86, 1984; L. Pereira, p. 383-404, in B. Roizman, ed., The herpesviruses, vol. 3, 1985), and two protein mixtures (58,000-molecular-weight [58K]-66K and 130K-66K), separated by serial columns prepared with anti-gA immunoglobulin G from sera of immunized guinea pigs, induced neutralizing antibodies and a cellular immune response in the animals. The gA is a disulfide-linked protein complex consisting of high-molecular-weight (greater than 200K), 130K-150K, and 55K-58K proteins.

Animals↗

Influenza virus-induced encephalopathy in mice: interferon production and natural killer cell activity during acute infection.

Mice injected intracerebrally with infectious influenza virus (60 hemagglutinin units) developed lethargy, seizures, comas, and died 2 to 5 days postinfection. As early as 6 h after infection, the cerebrospinal fluid (CSF) in these animals was infiltrated with polymorphonuclear cells, mononuclear leukocytes, and large granular lymphocytes. Potent natural killer (NK) cell activity was observed for both CSF and spleen cell populations over the same period. This NK cell activity correlated with interferon (IFN) levels in the CSF and serum. Treatment of lethally infected mice with either anti-IFN alpha-IFN beta or anti-ganglio-n-tetraoglyceramide antiserum ameliorated the disease, reduced mortality, and effected changes in the relative proportions of inflammatory cell populations infiltrating the CSF. The possible significance of IFN and NK cell activity in the development of this influenza virus-induced encephalopathy is discussed.

Animals↗

Varicella vaccine studies in healthy children and adults.

Immunization of normal children and adults with Oka strain live varicella vaccine from several manufacturers has been studied in our laboratory and elsewhere. This paper summarizes clinical trials designed to obtain information on minimum dose immunogenicity pre- and postexposure prophylaxis, immunization of various age groups, and booster immunizations for seropositive individuals. These studies documented a 94% to 100% seroconversion rate with 95% to 100% persistence of antibodies at 3 to 4 years. Protective efficacy was more than 90%, and the vaccine was successful in preventing varicella when a high dose was given postexposure. Clinical reactions were limited to temperature elevations and minor papulovesicular rashes that occurred in 5% to 10% of vaccinees. Herpes zoster has been absent in vaccinated healthy individuals.

Adult↗

The combination measles, mumps, rubella and varicella vaccine in healthy children.

A clinical trial was conducted to compare the combination measles, mumps, rubella, varicella vaccine (MMRV) and the standard measles, mumps, rubella vaccine and subsequent varicella vaccine (MMR + V) in 15 to 17 month old healthy children. Both the MMRV and MMR + V schedules stimulated virtually 100% seroconversion for all component viruses. Mean antibody titers were similar for each virus component in the two vaccine groups. Clinical reactivity post immunization was also similar with 25-29% morbilliform rashes, 12-25% mild papulovesicular (varicella) rashes, and 12.5-18% temperature elevations above 101 degrees F. Antibodies to measles, mumps, and rubella viruses were persistent in 8/10 originally seronegative MMRV vaccinees and 5/5 MMR + V recipients tested. On MMRV recipient had a household exposure to chickenpox during the year postvaccination that resulted in a subclinical boost in varicella antibody titer. Two children in the MMR + V group had close varicella exposures: one developed mild varicella (20 lesions). There were no known exposures to natural measles, mumps, or rubella. Three of four MMRV vaccinees with low titer antibody to varicella prior to immunization had greater than four-fold rises in antibodies. The combination measles, mumps, rubella, varicella vaccine is an immunogenic, safe and cost effective approach to varicella immunization of healthy children.

Antibodies, Viral↗

Combination measles, mumps, rubella and varicella vaccine.

A comparative clinical trial was conducted in 15- to 17-month-old healthy children to compare an investigational combination measles, mumps, rubella, varicella (MMRV) vaccine v standard measles, mumps, rubella vaccine followed 6 weeks later with the varicella (MMR + V) vaccine. Both the MMRV and MMR + V vaccine schedules stimulated virtually 100% seroconversion for all component viruses. Mean antibody titers were similar for each virus component in the two vaccine groups. Clinical reactivity postimmunization was also similar with 25% to 29% morbilliform rashes, 12% to 25% mild papulovesicular (varicella) rashes, and 12.5% to 18% temperature elevations above 38.3 degrees C (101 degrees F). Antibodies to measles, mumps, and rubella viruses were persistent at 1 year of follow-up in both groups. Varicella antibody was persistent in 8/10 originally seronegative MMRV vaccinees and 5/5 MMR + V vaccine recipients tested. One MMRV vaccine recipient had a household exposure to chickenpox during the year postvaccination that resulted in a subclinical boost in varicella antibody titer. Two children in the MMR + V vaccine group had close varicella exposures; mild varicella (20 lesions) developed in one. There were no known exposures to natural measles, mumps, or rubella. Three of four MMRV vaccinees with low titer antibody to varicella prior to immunization had greater than fourfold increases in antibodies after vaccination. The combination MMRV vaccine is an immunogenic, safe, and cost-effective approach to varicella immunization of healthy children. Continued work is needed to select the appropriate dose of varicella component, to assure higher persistence rate of varicella antibody.

Antibodies, Viral↗

Outbreak of cryptosporidiosis in a day-care center.

An outbreak of diarrhea due to infection with Cryptosporidium occurred in a day-care center. During a period of 2 months, 23 of 53 (43%) children attending the day-care center and 15 of 104 (14%) household contacts had diarrhea. Cryptosporidium oocysts were identified in 13 of 20 (65%) symptomatic children tested compared with three of 27 (11%) asymptomatic children (chi 2 = 12.56, P less than .001). Enteropathogenic bacteria, enteroviruses, rotavirus, and other protozoan parasites were ruled out as the cause of the diarrhea. A history of diarrhea in household contacts was associated with excretion of Cryptosporidium oocysts by the children. Human-to-human transmission of the infection was suggested by the epidemiology.

Child Day Care Centers↗

Imipenem/cilastatin for the treatment of infections in hospitalized children.

Imipenem is the first of a new class of beta-lactam antimicrobial agents with potent in vitro activity against most bacterial pathogens that cause infections in children. We studied, prospectively, the clinical efficacy and toxicity of imipenem/cilastatin in 40 children with proved or suspected bacterial infection. A dose of 100 mg/kg/day of imipenem was given to children younger than 3 years of age, while children older than 3 years of age received 60 mg/kg/day. Twenty-nine organisms were isolated from 26 patients. Infections treated included cellulitis, osteomyelitis, septic arthritis, lymphadenitis, renal infections, wound infections, and pneumonia. Bacteria isolated included Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Pseudomonas aeruginosa. All patients responded favorably to treatment, with defervescence and improvement of symptoms. All of the infecting bacteria were susceptible to imipenem. Imipenem/cilastatin was well tolerated, with no serious side effects, and appeared to be an effective and safe antimicrobial agent in the treatment of the population studied.

Arthritis, Infectious↗