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Biomedical subjects

S A Plotkin

Publications and source records attributed to S A Plotkin.

At least 19 recordsLinked to original sources
PubMed1991

Isolation and characterization of an infectious molecular clone of the MN strain of HIV-1.

Infectious molecular clones of the human immunodeficiency virus (HIV) have been very important tools for the analysis of regulatory gene functions and the study of differential cell tropism. We have cloned and characterized a proviral sequence of HIVmn from mn strain infected H9 cells. This clone, called KP1, was found to be infectious for different cell lines and human peripheral blood lymphocytes (PBL). KP1 proviral DNA was detected in HUT-78 cells and human PBL by polymerase chain reaction (PCR) analysis after infection of these cells with cell-free supernatants from KP1 transfected human rhabdomyosarcoma (RD) cells. To the best of our knowledge, this is the first report of an infectious molecular clone of HIVmn which is a representative of one of the most prevalent strains of HIV-1 in North America and Europe. Biologically active clones of a broadly antigenic strain such as HIVmn will be extremely useful in therapeutic approaches for AIDS.

Base Sequence↗
PubMed1991

Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. A controlled trial.

OBJECTIVE: To test the efficacy of vaccination with the Towne live attenuated cytomegalovirus vaccine. DESIGN: A double-blind, randomized, placebo-controlled trial in candidates for renal transplantation. The cytomegalovirus serologic status of both recipients and donors were determined, and the recipients were followed for periods of 6 months to 7 years after transplant. SETTING: A university transplant center. PATIENTS: The analyses were made on 237 patients who were given either vaccine or placebo, received renal transplants, and were followed for at least 6 months. INTERVENTION: Subcutaneous inoculation with Towne live attenuated virus or with placebo. MAIN OUTCOME MEASURES: The presence of cytomegalovirus infection was defined by virus isolation and antibody tests. If infection occurred, a prearranged scoring system for cytomegalovirus disease was used to objectify disease severity. RESULTS: The vaccine was well tolerated, and there were no discernible long-term adverse effects. Recipients who were originally seropositive did not clearly benefit from vaccination. Protective efficacy was analyzed in the group at highest risk for cytomegalovirus disease; recipients who were seronegative at the time of vaccination and who received a kidney from a seropositive donor. Compared with placebo recipients, vaccinated patients in this group had significantly less severe cytomegalovirus disease, with a significant reduction in disease scores (P = 0.03) and 85% decrease in the most severe disease (95% CI, 35% to 96%), although infection rates were similar. Graft survival at 36 months was improved in vaccinated recipients of cadaver kidneys (8 of 16) compared with unvaccinated recipients (4 of 16) (P = 0.04). CONCLUSIONS: Previous vaccination of seronegative renal transplant recipients with live cytomegalovirus results in reduction of disease severity mimicking the action of naturally derived immunity.

Adult↗
PubMed1991

Minitransfection: a simple, fast technique for transfections.

A fast, simple and inexpensive minitransfection technique, using either a lipofection or a calcium phosphate coprecipitation method to introduce foreign DNA into living cells is presented. This technique is based on the use of 24-well or 96-well tissue culture plates and can be used for both transient and stable transfections. Because it is a microtechnique, only small amounts of DNA, cells and transfection reagents are necessary, and it is easy to handle multiple DNA transfections or cotransfections in different cell lines and in duplicates or triplicates. The technique can be used to study viral gene expression, virus replication and chloramphenicol acetyltransferase (CAT) assay in different cell lines, for example, in the large scale screening and testing of antiviral agents.

Animals↗
PubMed1991

Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies.

A large double-blind, randomized, placebo-controlled trial of live attenuated Oka/Merck varicella vaccine was conducted among healthy children, 1-14 years of age. During the first varicella season, the efficacy of the vaccine among susceptible children was 100%1. During the second varicella season, 22 children were diagnosed with varicella; 21 cases in placebo recipients and one in a vaccine recipient. The overall efficacy of the vaccine through two varicella seasons was 98%. After the code for the study was broken, the original group of vaccine recipients continued to be followed for development of varicella. The estimated proportion of vaccine recipients who remained varicella-free at the end of 7 years was 95%. The 23 cases of varicella that occurred in vaccine recipients over the 7-year period were considerably milder than natural varicella. The average number of lesions was 53, 50% of the children had non-vesicular rashes, and 14% of the children had a temperature greater than or equal to 38.9 degrees C (102 degrees F), oral. The persistence of antibody in a subset of vaccine recipients followed for 6 years was 100%.

Adolescent↗
PubMed1991

Comparison of acellular and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants. The APDT Vaccine Study Group.

In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising.

Agglutination Tests↗
PubMed1991

Human immunodeficiency virus type 1 tat gene enhances human cytomegalovirus gene expression and viral replication.

Clonal lines of human rhabdomyosarcoma (RD) cells, constitutively expressing human immunodeficiency virus type 1 (HIV-1) tat gene (RD tat cell lines) showed enhanced expression of human cytomegalovirus (HCMV) immediate-early (IE) and late (L) proteins upon HCMV infection, as compared with control RD cells. One of the RD tat cell lines produced infectious HCMV. The RD-tat cell lines, following transfection with recombinant plasmids containing the full length of the HCMV-IE enhancer/promoter linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, exhibited an increased CAT expression by the tat product. A chronically HIV-1-infected human T-lymphoid cell line, SupT1, superinfected with HCMV, expressed HCMV-IE proteins while the parental SupT1 cells infected with HCMV were negative. Parental SupT1 cells coinfected with HIV-1 and HCMV also expressed HCMV-IE proteins, indicating that HIV-1-encoded proteins exert a positive regulatory effect on HCMV expression.

Antigens, Viral↗
PubMed1991

Current issues in evaluating the efficacy of oral poliovirus vaccine and inactivated poliovirus vaccine immunization.

Although epidemic poliomyelitis in the United States has been eliminated, there are a number of current issues that concern the use of oral attenuated poliovirus vaccine in comparison with the new enhanced-potency inactivated vaccine. Although wild-type poliovirus is almost eradicated in developed nations, vaccine-induced polio exists, at a low but persistent rate. This article reviews the current issues and suggests a return to the Institute of Medicine's 1988 recommendations concerning combined immunization with inactivated poliovirus vaccine and oral poliovirus vaccine.

Humans↗
PubMed1991

Differentiation of human embryonal carcinoma cells induces human immunodeficiency virus permissiveness which is stimulated by human cytomegalovirus coinfection.

Human immunodeficiency virus (HIV) replicates in differentiated but not undifferentiated NTERA-2 human embryonal carcinoma cells; neither cell type expresses CD4. Susceptibility of the differentiated cells is enhanced by coinfection with cytomegalovirus. HIV infection induces lactoseries glycolipids, suggesting a mechanism whereby HIV might interfere with normal embryogenesis.

Antibodies, Monoclonal↗
PubMed1991

Protracted mononucleosis-like illness associated with acquired cytomegalovirus infection in a previously healthy child: transient cellular immune defects and chronic hepatopathy.

Ordinarily, severe disease due to acquired cytomegalovirus (CMV) infection does not occur in immunocompetent children. We describe a previously healthy boy who acquired primary CMV infection at approximately 2 years of age and experienced a 2-year-long debilitating multisystem illness from which he ultimately recovered. Clinical features of this illness included fatigue, poor weight gain, pallor, unexplained fever, musculoskeletal complaints, drenching night sweats, lymphadenopathy, and massive hepatosplenomegaly. Laboratory abnormalities included elevated erythrocyte sedimentation rate, lymphocytosis, and elevated immune complex levels. Cellular immune function was impaired during the illness but was demonstrably normal during convalescence, and there was no other evidence for a known immunodeficiency state. Immunoblot analysis showed enhanced antibody response to a 66-kd infected cell protein after symptomatic recovery. Despite consistently normal indices of hepatic function, liver enlargement persisted after other symptoms had resolved. Liver biopsy demonstrated a mononuclear cell portal tract infiltrate with fibrosis, but CMV could not be demonstrated directly in this tissue. Primary CMV infection has not been reported previously to cause the persistent symptoms seen in this child.

Biopsy↗
PubMed1990

Serotype 1 reassortant of bovine rotavirus WC3, strain WI79-9, induces a polytypic antibody response in infants.

A reassortant rotavirus, strain W179-9, was constructed bearing gene 9 of serotype 1 rotavirus strain WI79 and all other genes derived from bovine (serotype 6) rotavirus strain WC3. The antigenic phenotype of WI79-9 is bivalent: serotype 1 and serotype 6. WI79-9 administered orally at a dose of 10(7.5) p.f.u. induced no adverse effects in 48 infants of age 2-11 months. Serotype 1- and serotype 6-specific serum neutralizing antibody titres were induced with approximately equal frequency in these infants. Serotype 1-specific antibody responses were inhibited in infants previously seropositive to type 1. The immune response rate was enhanced by administration of a second, 'booster dose'.

Adult↗
PubMed1990

Immune protection of infants against rotavirus gastroenteritis by a serotype 1 reassortant of bovine rotavirus WC3.

The safety and protective efficacy of a serotype 1 reassortant of bovine rotavirus WC3, disignated strain WI79-9, was evaluated in a double-blind placebo-controlled trial. Rotavirus reassortant WI79-9 contains a gene segment 9 coding for the surface structural protein vp7 of a human serotype 1 rotavirus, with all other gene segments derived from WC3 rotavirus, which had previously been shown to be safe and immunogenic in infants. Infants 2-11 months of age were given two doses of vaccine (10(7.3) plaque-forming units/dose) or of placebo 28 days apart. Adverse reactions to the vaccine were not detected. The incidence of serum plaque reduction neutralization antibody responses to two doses of vaccine was serotype 6, 97%; serotype 3, 68%; and serotype 1, 22%. Active surveillance during the subsequent rotavirus season revealed 8 cases of rotavirus gastroenteritis in 39 placebo control infants and no cases in 38 WI79-9 vaccine recipients (protection = 100%, P = .003). Six cases of rotavirus gastroenteritis were caused by type 1 and two by type 3 virus. Although vaccination with WI79-9 affected only the incidence of rotavirus gastroenteritis, the vaccinated infants exhibited a significantly reduced incidence of total days of diarrhea, fever, and illness associated with gastroenteritis in general.

Antibodies, Viral↗
PubMed1990

An adenovirus recombinant that expresses the human cytomegalovirus major envelope glycoprotein and induces neutralizing antibodies.

The gene of the human cytomegalovirus (HCMV) major envelope glycoprotein, gB, was cloned from the Towne strain and inserted into adenovirus type 5 downstream of the E3 promoter. The recombinant virus, Ad-gB, expressed antigenically related proteins of 58, 30, 25, and 23 kDa in A549 and MRC-5 cells; the 58-kDa protein had the same mobility as the native gB from HCMV-infected MRC-5 cells and virions. All four proteins were detected by a monospecific polyclonal antiserum and by a monoclonal antibody in immunoblot and immunofluorescence assays. Hamsters infected intranasally with live Ad-gB developed protein-specific and HCMV-neutralizing antibody. This study confirms the importance of gB in the generation of the neutralizing immune response to HCMV and demonstrates the potential of live adenoviruses as vaccine vectors.

Adenoviruses, Human↗