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Biomedical subjects

S A Plotkin

Publications and source records attributed to S A Plotkin.

At least 145 records · Page 8Linked to original sources

Effect of DNA polymerase inhibitors on the replication of human cytomegalovirus. Brief report.

Aphidicolin, a specific inhibitor of cellular DNA polymerase alpha and of viral DNA polymerase, inhibits production of infectious virus and cellular and viral DNA synthesis of human cytomegalovirus (HCMV)-infected cells. On the other hand, 2',3'-dideoxynucleosides, inhibitors of DNA polymerases beta and gamma, do not affect HCMV replication. The data show that the alpha DNA polymerases of either viral or cellular origin are required for viral DNA synthesis, and cannot be substituted by the cellular DNA polymerase beta and gamma.

Aphidicolin↗

Preparation of highly purified human cytomegalovirus envelope antigen.

A human cytomegalovirus (HCMV) envelope preparation was highly purified by immunoaffinity column chromatography using an anti-cellular-IgG column. The purified envelope induced high titre antibodies to HCMV in guinea-pigs. Analysis of the guinea-pig immune sera by RIA and immunofluorescence (IF) showed that this envelope preparation, unlike its unpurified counterpart, did not induce antibody to cellular contaminants. Dot-blot assay revealed viral proteins in the flow-through fraction and cellular proteins in the bound fractions. Results of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of flow-through and bound fractions suggest that a number of proteins previously identified as virus-specific may, in fact, reflect cellular contamination of the envelope preparation, or crossreactivity of some virus-specific proteins with cellular proteins.

Animals↗

The role of pretransplant immunity in protection from cytomegalovirus disease following renal transplantation.

To determine the extent to which pretransplant immunity resulting from natural infection protects against cytomegalovirus (CMV) disease, we analyzed CMV serology on 153 kidney donor and recipient pairs and followed transplant patients to determine incidence and severity of CMV disease. The overall incidence of CMV disease was 22%. Significant differences occurred in CMV disease incidence and severity, depending on the immune status of the kidney donor and recipient. Among recipients of kidneys from seropositive donors, immunity offered significant protection from CMV disease, reducing its incidence from 61% in nonimmune to 24% in immune patients (P less than 0.01). Pretransplant immune patients also had fever CMV-related complications. Among recipients of kidneys from seronegative donors, pretransplant immunity conferred a significant risk of CMV disease; immune patients had a 20% incidence of CMV disease compared with 2% in nonimmune patients (P less than 0.02). Disease was generally mild in all patients receiving kidneys from CMV infection had a 3-fold higher incidence of CMV disease than patients with reactivation infection (P less than 0.01). The incidence of CMV disease was similar in immune patients, whether they received a kidney from a seropositive or a seronegative donor. However, an important observation was that disease was significantly more severe in immune patients receiving a kidney from a seropositive donor (P less than 0.05). This indicates that if kidneys from seropositive donors are selected for use only in seropositive recipients, this places the immune patient at a higher risk for severe CMV disease. We conclude that pretransplant immunity offers a significant advantage to patients receiving kidneys from seropositive donors.

Adolescent↗

Cytomegalovirus infection of human teratocarcinoma cells in culture.

Whereas human cytomegalovirus (HCMV) did not replicate in human embryonal carcinoma (EC) cells, it did replicate in some of the differentiated cells arising following the exposure of TERA-2-derived human EC cells to retinoic acid. On the other hand, retinoic acid did not induce a permissive state in several other diverse human cell lines, including an EC line, 2102Ep, which did not differentiate in response to this agent. Also, both TERA-2 and 2102Ep EC cells differentiated to a limited extent when grown at low cell density and a few of these cells became permissive for HCMV. Thus, susceptibility is the result of differentiation and not due to a direct effect of retinoic acid on viral replication. The nature of the block to HCMV replication in human EC cells is unknown, but viral DNA could be detected in the nucleus within an hour of infection and there was an increased anchorage-independent growth of undifferentiated and differentiated cells following HCMV infection. Viral replication is not subject to a general block in these cells, since another herpesvirus, herpes simplex virus type 1, replicated well.

Cell Adhesion↗

Epidemiology of rotavirus electropherotypes determined by a simplified diagnostic technique with RNA analysis.

The incidence and RNA electropherotypes of rotavirus in stools or rectal swabs of children with diarrhea were studied for three rotavirus seasons (1981 through 1984) in Philadelphia, Pa. We used a simplified RNA analysis method involving polyacrylamide gel electrophoresis followed by silver staining. Phosphate-buffered saline suspensions of the stools and swab eluates were examined directly by polyacrylamide gel electrophoresis-silver staining analysis and enzyme-linked immunoadsorbent assay (Rotazyme; Abbott Laboratories); electron microscopy was performed on solid stool specimens. The RNA analysis results were compared with electron microscopy and enzyme-linked immunosorbent assay results and exhibited a sensitivity and specificity greater than or equal to that of electron microscopy or the enzyme-linked immunosorbent assay. Ten different electropherotypes were detected among the 68 rotavirus RNA-positive specimens examined over the 3-year study. The predominant electropherotype was different in each season. Our results indicate that the polyacrylamide gel electrophoresis-silver nitrate strain RNA analysis of simple unextracted stool suspensions is a uniquely useful diagnostic technique; it rapidly provides both a definitive positive result and immediate determination of the RNA electropherotype, which is of value for epidemiological study.

Electrophoresis, Polyacrylamide Gel↗

The future of varicella vaccine.

Based on conservative figures, an estimated 60 million varicella-zoster cases occur annually worldwide, highlighting the global significance of this disease. The development of a viable varicella vaccine, therefore, raises important questions as to the indications for its use in normal children, normal seropositive and seronegative adults, and immunocompromised patients. A review of the available data addresses the potential future role of the varicella vaccine in these groups.

Chickenpox↗

Clinical and pathogenetic aspects of varicella-zoster.

In this review article the pathogenetic mechanisms of infection with the varicella-zoster virus (VZV) and its short- and long-term clinical consequences are discussed. It is concluded that the impact of VZV is severe enough to seriously consider widespread immunization against it.

Adult↗

Routine quantitative blood cultures in children with Haemophilus influenzae or Streptococcus pneumoniae bacteremia.

The potential clinical value of quantitative blood cultures determined by a commercially available lysis-direct plating method was studied in 50 children with either Haemophilus influenzae or Streptococcus pneumoniae bacteremia. The magnitude of bacteremia correlated with the severity of the infection; patients with greater than or equal to 100 colony-forming units per milliliter were significantly more likely to have meningitis (P less than .01, chi 2 = 7.5). On the other hand, all patients with S. pneumoniae bacteremia with colony counts lower than 15 colony-forming units per milliliter had "occult bacteremia" with no focus of infection. The data suggest that patients with higher levels of bacteremia have more severe disease. Quantitative blood culture results may be helpful in identifying which children are at risk for invasive disease.

Colony-Forming Units Assay↗

Cytomegalovirus replicates in differentiated but not in undifferentiated human embryonal carcinoma cells.

To study the mode of action of human cytomegalovirus, an important teratogenic agent in human populations, the susceptibility of a pluripotent human embryonal carcinoma cell line to the virus was investigated. Viral antigens were not expressed nor was infectious virus produced by human embryonal carcinoma cells after infection, although the virus was able to penetrate these cells. In contrast, retinoic acid-induced differentiated derivatives of embryonal carcinoma cells were permissive for antigen expression and infectious virus production. Replication of human cytomegalovirus in human teratocarcinoma cells may therefore depend on cellular functions associated with differentiation.

Cell Line↗

Towne-vaccine-induced prevention of cytomegalovirus disease after renal transplants.

91 renal transplant candidates were randomised to receive Towne strain cytomegalovirus (CMV) vaccine or placebo at least 8 weeks before transplantation. The vaccine was well tolerated and there was no vaccine virus excretion. Serological and cellular immune responses developed in most vaccines but were lower in the transplant patients than in healthy volunteers and some of the seronegative patients failed to mount responses. CMV infection occurred in most of the seronegative vaccine-treated or placebo-treated patients who received kidneys from seropositive donors, but the illnesses were less severe in the vaccines than those in similarly exposed placebo-treated patients. Vaccine-treated patients who received kidneys from seronegative donors did not excrete virus, and therefore the vaccine virus was not reactivated from a putative latent state despite immunosuppression at the time of transplantation.

Antibodies, Viral↗

Vancomycin dosage in pediatrics reconsidered.

Vancomycin hydrochloride levels were studied in 44 children (age range, 10 days to 10 years). These children received doses of vancomycin within current recommendations. Major variations in vancomycin levels were demonstrated in similar age groups and dosage regimens. For patients in the first month of life, second month of life, and older ages, respectively, 70%, 39%, and 30% of the peak determinations and 53%, 50%, and 23% of the trough determinations were greater than the desired level. Potentially toxic levels were found in eight patients.

Age Factors↗