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Biomedical subjects

S E Starr

Publications and source records attributed to S E Starr.

At least 91 records · Page 5Linked to original sources
PubMed1984

Natural killing of cytomegalovirus-infected targets in renal transplant recipients.

The ability of peripheral blood mononuclear cells of renal transplant recipients to lyse cytomegalovirus (CMV) infected fibroblasts was determined in an 18-hr 51Cr release assay. Natural killing (NK) against CMV-infected targets was generally depressed for the first two years after transplantation. In three individuals who developed CMV disease after transplantation, NK activity against CMV-infected and uninfected targets rose to high levels following reductions in immunosuppressive therapy and in temporal association with resolution of disease.

Adult↗
PubMed1984

Susceptibility of vaccine strains of varicella-zoster virus to antiviral compounds.

Using a plaque reduction assay, we determined the 50% effective doses of six antiviral compounds against low- and high-passage viruses of the KMcC and Oka strains of varicella-zoster virus vaccine. The potency, as indicated by the ranges of 50% effective doses (micrograms per milliliter) of the antiviral compounds, in decreasing order was as follows: (E)-5-(2-bromovinyl)-2'-deoxyuridine, 0.0007 to 0.0035; 1-(2'-flouro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine, 0.0063 to 0.0091; aphidicolin, 0.092 to 0.180; acyclovir, 0.79 to 1.81; vidarabine, 0.62 to 2.10; and phosphonoformic acid, 8.18 to 16.4. Susceptibility to the various antiviral compounds was independent of passage level or strain. These data, along with the available in vivo data, indicate that varicella-zoster virus vaccine infections requiring antiviral therapy most probably would be treated as effectively as would natural varicella infections.

Antiviral Agents↗
PubMed1984

Human polymorphonuclear leukocyte-mediated cytotoxicity against varicella-zoster virus-infected fibroblasts.

Polymorphonuclear leukocytes (PMN) were studied for their ability to mediate cytotoxicity against varicella-zoster virus (VZV)-infected and uninfected human fibroblasts in 51Cr release assays. PMN were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) against VZV-infected targets. Maximal ADCC was obtained with effector-to-target ratios of 100:1 and 18 h of incubation. Percent 51Cr release for 26 normal adults was 14.1 +/- 0.6 (mean +/- standard error) in the presence of pooled human seropositive sera (final dilution, 1:100) and 0.5 +/- 0.6 in the presence of pooled human seronegative sera. Addition of phorbol myristate acetate (PMA) enhanced PMN-mediated cytotoxicity against VZV-infected and uninfected targets. PMA-stimulated cytotoxicity was optimal with PMA concentrations of 200 ng/ml and effector-to-target ratios of 10:1, and antibody was not required; killing was detected as early as 3 h after incubation and was maximal after 18 h. Highly purified PMN were capable of mediating both ADCC and PMA-stimulated lysis. Catalase completely inhibited PMA-stimulated PMN cytotoxicity, but had no effect on PMN-mediated ADCC. PMN from patients with chronic granulomatous disease were capable of mediating ADCC, but not PMA-stimulated killing, against VZV-infected targets. Thus, PMN could kill VZV-infected targets by two different mechanisms: ADCC, which required antibody but not hydrogen peroxide (H2O2), and PMA-stimulated cytotoxicity, which required H2O2 but not antibody.

Adult↗
PubMed1983

Live attenuated varicella vaccine: the KMcC strain in healthy children.

The KMcC strain of live, attenuated varicella-zoster virus vaccine was studied in healthy children as a preliminary step toward varicella vaccine studies with this strain in children with leukemia. Forty-three children were immunized: 26 with the 40th passage vaccine and 17 with the 50th passage. Studies included surveillance for clinical reactivity, oropharyngeal excretion of vaccine virus, viruria, and viremia. Antibody responses were assayed by fluorescent antibody to membrane antigens and immune adherence hemagglutination. Cell-mediated immune responses were assayed by lymphocyte proliferation to varicella-zoster virus specific antigens. There was 100% seroconversion to the KMcC passage 40 and 50 vaccines (by fluorescent antibody to membrane antigen assay). Every child studied developed in vitro lymphocyte proliferation to varicella-zoster virus antigens. Papular skin lesions, probably vaccine related, occurred in 31% of the 40th passage vaccinees but in only 6% of the 50th passage vaccinees. The 50th passage KMcC strain vaccine is sufficiently immunogenic and safe to initiate clinical studies with leukemia patients.

Adolescent↗
PubMed1982

In vitro and in vivo responses of cytomegalovirus to acyclovir.

Laboratory strains and fresh isolates of human cytomegalovirus (HCMV) were tested for sensitivity to acyclovir. Fifty percent inhibition was achieved at about 10 micrograms/ml, but 25 to 100 micrograms/ml was necessary for 90 percent or greater inhibition. Acyclovir was administered intravenously to four patients with congenital cytomegalovirus (CMV) infection. There was only a temporary diminution of virus titer in the urine and no obvious clinical improvement. One child experienced hematuria. Pharmacokinetic studies showed a large volume of distribution and slow excretion of acyclovir with a half-life of approximately three hours.

Acyclovir↗
PubMed1982

Acyclovir treatment of herpes zoster infections. Use in children undergoing bone marrow transplantation.

Three patients in whom herpes zoster infections developed following bone marrow transplantation were treated with acyclovir. The patients experienced pain relief within 24 hours of starting treatment. The progression of their skin lesions halted within 1, 2, and 4 days of therapy, respectively, and healed completely within two weeks of therapy. Pharmacokinetic studies indicated that acyclovir plasma concentration-time profiles approximated biexponential equations. The drug half-lives were 3.91, 3.83, and 3.40 hours, respectively. Acyclovir was not myelotoxic and may be helpful in aborting varicella-zoster virus infections in bone marrow transplant recipients.

Acyclovir↗
PubMed1982

Vaccination of pediatric nurses with live attenuated cytomegalovirus.

Congenital cytomegalovirus (CMV) infections contribute considerably to morbidity and mortality among infants in the United States. In a preliminary study aimed at protecting fetuses from congenital disease we evaluated Towne 125-strain CMV vaccine in ten female pediatric nurses of childbearing age. The women were seen 2, 4, 8, 12, 26, 39, and 52 weeks after vaccination; specimens were obtained for routine laboratory testing, virus isolation, cell-mediated immunity testing, and serologic examination (complement fixation, anticomplement immunofluorescence [ACIF], and neutralization). Local but not systemic reactions were observed in all subjects. Serologic responses appeared at two to four weeks and peaked at four to eight weeks. Mean titers were highest in the ACIF test. A cell-mediated immune response, as assayed by lymphocyte proliferation, was observed in all women, and in most there was a biphasic pattern. Towne 125-strain CMV vaccine seems to be safe and immunogenic in women of childbearing age.

Adult↗
PubMed1982

Live attenuated varicella vaccine: immunization of healthy children with the OKA strain.

Ninety-one healthy children were immunized with one of three preparations of the OKA strain of live attenuated varicella zoster virus in order to gain sufficient information on safety and immunogenicity to justify vaccine studies in immunosuppressed children. The OKA-Biken vaccine was studied in a dose response trial. Two additional clinical trails were conducted with the OKA strain that was further passaged: a frozen aqueous (OKA-RIT-Aq) form and a lyophilized (OKA-RIT-Ly) form were tested. With each of these vaccines clinical reactivity was minimal and virus shedding, viremia, and transmission of the vaccine virus were absent. Excellent seroconversion rates of 100 and 94% were induced with approximately 500 pfu of OKA-Biken and OKA-RIT-Ly vaccine, respectively. A lower seroconversion rate was noted for OKA-RIT-Aq, presumably on the basis of defective individual vials. Diluted OKA-Biken vaccine induced less seroconversion but even the 5 pfu dose produced antibody responses in 81% of the vaccinees. In vitro specific cellular immune responses to varicella virus antigens were demonstrated in each group of vaccinees, including all but two of those vaccines who failed to seroconvert. The data indicate that two preparations of the OKA strain are sufficiently safe and immunogenic in healthy children to support further studies in immunocompromised children.

Antibodies, Viral↗
PubMed1982

Antibody-dependent cell-mediated cytotoxicity against varicella-zoster virus-infected targets.

Antibody-dependent cell-mediated cytotoxicity (ADCC) against cryopreserved varicella-zoster virus-infected human foreskin fibroblasts was detected in a 51Cr release assay. Target cells, samples of seropositive or seronegative sera, and mononuclear cells obtained by Ficoll-Hypaque centrifugation of human peripheral blood were added to microtiter plate wells and allowed to incubate at 37 degrees C for 4 h. Fibroblasts infected for 48 to 96 h were susceptible to ADCC. Effector cells from seropositive and seronegative normal children were equally active in the assay. Antibody titers were determined by testing serial dilutions of sera in the ADCC assay. Zoster immune globulin had a titer of 204,800. Sera from 40 naturally seropositive individuals were compared by assays for ADCC and fluorescent antibody to membrane antigen. All sera that were negative by fluorescent antibody to membrane antigen (less than 2) were also negative by ADCC (less than 20). All sera that were positive by fluorescent antibody to membrane antigen were also positive by ADCC, but titers of individual sera were frequently 5 to 20 times higher in the ADCC assay.

Antibodies, Viral↗
PubMed1981

Specific cellular and humoral immunity after immunization with live Towne strain cytomegalovirus vaccine.

Cytomegalovirus-specific lymphocyte proliferation and immunofluorescent antibody responses were measured serially in five normal adults and eight candidates for renal transplant immunized with Towne strain cytomegalovirus vaccine. All of the normal adults developed cellular and humoral immune responses. Five of the eight immunized renal transplant candidates developed proliferative responses comparable to those of normal adults, although in two instances maximal responses were delayed. Vaccinees developed proliferative responses to antigens prepared from the Towne strain as well as heterologous strains of cytomegalovirus. The appearance of immunofluorescent antibodies was generally delayed for the renal transplant candidates, and two of the individuals who had poor proliferative responses also had low antibody titers.

Antibody Formation↗
PubMed1981

Natural killing of cytomegalovirus-infected fibroblasts by human mononuclear leucocytes.

The ability of human peripheral blood mononuclear (MN) cells to lyse uninfected and cytomegalovirus (CMV) infected human fibroblasts was determined in a 51Cr-release assay. Maximal release was obtained with 6-day infected fibroblasts incubated with MN cells for 24 hr. A linear relationship existed between E/T ratios of 12.5:1 to 100:1 and lysis of CMV-infected targets. Donor immune status had no effect on the magnitude of killing of infected or uninfected targets. Killing was mediated by non-B, predominantly non-T, Fc receptor-bearing cells. Preincubation of effector cells with interferon enhanced killing of both CMV-infected and uninfected fibroblasts, but infected targets were more effectively killed. These results indicated a possible role for natural killer cells in recovery from CMV infection.

Adult↗
PubMed1981

Tuberculosis presenting as an orbital mass.

A 15-year-old male adolescent underwent surgical exploration for a mass lesion of the left orbit. Orbital and pulmonary tuberculosis were postoperatively diagnosed on the basis of radiologic and histopathologic findings, a positive tuberculin skin test reaction, and positive cultures for Mycobacterium tuberculosis. This case emphasizes the point that tuberculosis should be considered in the differential diagnosis of orbital masses.

Adolescent↗
PubMed1980

Inactivated mouse cytomegalovirus vaccine: preparation, immunogenicity, and protective effect.

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.

Animals↗
PubMed1980

Lymphocyte blastogenesis and interferon production in adult human leukocyte cultures stimulated with cytomegalovirus antigens.

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.

Antigens, Viral↗
PubMed1979

Cytomegalovirus.

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Adult↗