Biomedical subjects
Publications and source records attributed to S A Plotkin.
A human osteogenic sarcoma cell culture is useful in the immunofluorescence serological test for detecting human cytomegalovirus antibody. These sarcoma cells are chronically infected with human cytomegalovirus and provide a constant number of immunofluorescence-positive cells.
Four human hepatoma cell lines established from primary hepatocellular carcinomas were examined for the presence of hepatitis B virus DNA sequences. Reassociation kinetic analysis indicated that the cell lines HEp-3B 217, HEp-3B 14, HEp-3B F1, and PLC/PRF/5 contained two, one, one, and four genome equivalents per cell, respectively. Southern blot hybridization analysis demonstrated that hepatitis B virus DNA was integrated into the cellular DNAs of these cell lines. Further liquid hybridization studies with 32P-labeled HincII restriction fragments of hepatitis B virus DNA established that DNA sequences from all regions of the HBV genome were represented in the integrated viral sequences. Although the three HEp-3B cell lines were derived from the same tumor, they differed significantly in their patterns of integration of hepatitis B virus DNA, the number of copies of viral DNA per cell, and their ability to produce the virus-coded surface antigen.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Three children are described with osteomyelitis confirmed by roentgenogram, blood culture, bone culture, and/or histologic findings. None had an abnormal technetium scintigram. Despite the lack of falsely normal bone scans for osteomyelitis reported in the literature, our cases demonstrate the importance of instituting antibiotic therapy on the basis of clinical suspicion since no single nonsurgical procedure can be relied on to make a diagnosis of osteomyelitis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Mouse cytomegalovirus (CMV) was rapidly and completely inactivated at 37 C by formalin diluted 1:4,000. Of 18 mice that received two doses of inactivated mouse CMV, 16 survived challenge with 250% lethal doses of mouse CMV; one of 11 mice receiving two doses of a control preparation survived the challenge (P < 0.005). After challenge with live virus, recognizable morbidity occurred in only four of 16 recipients of inactivated mouse CMV, but the virus was recovered from the salivary glands of 15 animals. Mice with reciprocal prechallenge titers of neutralizing antibody of < 4 demonstrated significantly higher morbidity and mortality than mice with higher antibody titers. Administration of inactivated mouse CMV did not depress responsiveness of spleen cells to phytohemagglutinin. Most mice immunized with inactivated virus developed only mild or subclinical infections after challenge with lethal doses of mouse CMV.
Lymphocyte blastogenesis and interferon production were measured in adult human leukocyte cultures stimulated with purified or crude cytomegalovirus antigens. Leukocytes from seropositive adults underwent blastogenesis when stimulated with purified or crude Towne strain antigen, whereas neither antigen stimulated blastogenesis in cultures from seronegative donors. The concentrations of antigens yielding maximal blastogenesis varied among the individuals tested. When cultures from seropositive individuals were stimulated with antigens prepared from three different CMV strains--AD-169, Towne, and Davis--comparable levels of blastogenesis were detected. Type 1 interferon was detected in supernatants of cultures stimulated with crude antigens regardless of the immune status of the donor. In contrast, when purified antigen was used as the stimulant, only cultures obtained from seropositive individuals produced detectable levels of interferon, which appeared to be predominantly type 2 or immune interferon.
Although infrequently an antibiotic of first choice for neonates, chloramphenicol (CL) may be indicated in selected instances of infection caused by aminoglycoside-resistant enterobacteriaciae, anaerobes, and ampicillin-resistant Haemophilus influenzae. Use of CL in neonates has been limited since the recognition that vascular collapse may occur as a consequence of dosage regimens tolerated by adults. With an assay that detects only active CL, we studied drug disposition in 13 low birth weight infants, eight between 1 and 8 days of age (group I), and five between 11 days and 8 weeks of age (group II). Peak serum CL concentrations ranged from 11.2 to 36.2 microgram/ml in group I and from 10.0 to 36.2 microgram/ml in group II, at doses ranging from 15 to 50 mg/kg/day, and 25 to 50 mg/kg/day, in groups I and II, respectively. Serum CL half-lives (T1/2) ranged from 10 to 36 hours in four of the eight group I patients; three of the remaining patients had T1/2 greater than 48 hours and the fourth patient accumulated CL in the interval between doses. T1/2 in group II ranged from 5.5 to 15.7 hours. Observed differences in T1/2 between groups I and II were statistically significant (P = .05) and could not be accounted for by factors other than postnatal age. These preliminary data suggest that although there appears to be an inverse relationship between CL T1/2 and postnatal age, there is sufficient variability in serum levels that monitoring must be performed in low birth weight infants treated with this drug.
Explore the source record for details and available documents.
Cells from a line of human lymphocytes originating from a leukemic patient were persistently infected with human cytomegalovirus. Assays of infectious centers and fluorescent antigen staining indicated that 1%--10% of the cells were infected. It appears that persistent infection is due to an equilibrium between the release of virus by infected host cells and the growth of uninfected cells rather than to defective virus or temperature-sensitive mutants.
Two cases of relapse of pneumonia caused by cytomegalovirus (CMV) in recipients of renal transplants were studied. Between episodes of pneumonia, both patients recovered completely as judged by X-ray clearing and by resolution of fever and respiratory symptoms. CMV was isolated during each episode of pneumonia from lung tissue, pleural fluid, or buffy coat cultures. Serologic studies revealed a rise in titer of antibody, confirming recent infection with CMV during the first epidose of pneumonia in each patient. Intranuclear inclusions consistent with CMV infection were detected in each of the three episodes where lung tissue was obtained. Special stains and cultures for Pneumocystis carinii, fungi, Nocardia, and mycobacteria yielded negative results. The renal allograft continued to function in both patients after they recovered from the first bout of pneumonia, and the relapse was temporally related to reinstitution of aggressive immunosuppressive therapy. The relapse of pneumonia emphasizes the need for caution when immunosuppressive therapy is reinstituted after recovery from serious CMV infection.
Cell-mediated immunity to cytomegalovirus (CMV) was determined in congenitally infected children and their mothers by use of assays for CMV-specific lymphocyte blastogenesis and interferon production. Six viruric children responded poorly in both assays. Two older nonviruric children responded in the blastogenesis assay, and lymphocytes from one of them produced interferon. Mothers of older children usually responded in the blastogenesis assay, but only one of them produced interferon. Mothers whose infected infants were younger than nine months of age responded poorly in both assays, while control seropositive postpartum women generally responded normally. The cell-mediated immune defects detected in this study may play a role in the pathogenesis of congenital CMV infection.
Significant morbidity and mortality are associated with primary cytomegalovirus infections in renal-transplant recipients. In the hope that immunity to cytomegalovirus could safely be established before transplantation, we vaccinated 12 seronegative renal-transplant candidates with the Towne 125 strain of live human cytomegalovirus. Before transplantation, there were no significant reactions except for erythema and induration at the site of inoculation. All vaccinees seroconverted, and the three patients tested acquired a cytomegalovirus-specific cellular immune response. Ten vaccinees underwent transplantation: Nine have completed at least 3 months of follow-up, and eight retain functioning allografts up to 1 year later. Although cytomegalovirus was isolated from six patients after transplantation, the restriction endonuclease patterns of the viral DNA of four of these isolates differed significantly from those of the vaccine strain. Therefore, it appears that the vaccine strain did not become latent in the host, at least in a form that could be reactivated.