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B S Graham

Publications and source records attributed to B S Graham.

At least 19 recordsLinked to original sources
PubMed1992

Serum antibodies to HIV-1 in recombinant vaccinia virus recipients boosted with purified recombinant gp160. NIAID AIDS Vaccine Clinical Trials Network.

Serum antibody responses were studied in detail in four vaccinia-naive volunteers in a phase I trial evaluating primary vaccination with a recombinant vaccinia virus expressing the HIV-1 gp160 envelope glycoprotein (HIVAC-1e, Oncogen/Bristol-Myers Squibb), followed by booster immunization with baculovirus-derived rgp160 (VaxSyn, MicroGeneSys). Prior to boosting, low-titer Fc receptor (FcR)-mediated, antibody-dependent enhancing (ADE) activity was detected in two of four volunteers but no IgM, IgG, IgA, neutralizing activity, or complement-mediated ADE activity was detected. Two weeks after boosting, all four volunteers developed HIV-1-specific IgG with titers of 1:160 to 1:640 by immunofluorescence assay. IgG1 was present in sera from each individual, while IgG2 and IgG3 were present in sera from two individuals, and IgG4 was present in serum from one individual. IgM and IgA were undetectable in all sera. Only one volunteer had IgG to the heterologous HIV-1 isolates, RF, MN, and SF2, after boosting. Serum from this volunteer neutralized the vaccine strain, LAV/IIIB, but not the heterologous strains, RF, MN, and SF2. Antibodies from the remaining volunteers had no neutralizing activity. The neutralizing serum had a positive reaction in a peptide-based ELISA utilizing a peptide corresponding to the principal neutralizing domain of the third hypervariable region (i.e., V3 loop) of the envelope glycoprotein. Neutralizing activity was partially removed by adsorption to this peptide, suggesting that it contained a type-specific neutralizing vaccine epitope. A low titer (1:40 to 1:80) of complement-mediated ADE activity to HIV-1 IIIB was present in sera from three vaccinees after boosting. FcR-ADE activity for HIV-1 SF2 and SF-128A were present in sera from two of these three vaccinees. None of the volunteers developed antisyncytial antibodies. These results indicate that inoculation with recombinant vaccinia followed by rgp160 boosting is the most effective strategy to date for inducing serum antibodies to the envelope glycoproteins of HIV-1, but further study is needed to optimize the functionality and cross-reactivity of these responses.

AIDS Vaccines↗
PubMed1992

Acute pubic osteomyelitis in athletes.

Three cases of pubic osteomyelitis in athletes are reported. The clinical presentation in each case was acute groin, hip, or perineal pain; fever; chills; inability to bear weight; and pubic symphysis tenderness. Since radiographic changes in the pubic bone can be delayed, a high index of suspicion is required by the clinician. Although Staphylococcus aureus is the dominant pathogen in pubic osteomyelitis, it is recommended that the diagnosis be established by culture of blood or pubic bone aspirate so that specific therapy can be instituted quickly.

Acute Disease↗
PubMed1992

Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network.

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160-specific immune responses.

AIDS Vaccines↗
PubMed1992

Perinatal transmission of human immunodeficiency virus-1 infection and maternal immunization strategies for prevention.

OBJECTIVES: To review the current understanding of the epidemiologic and pathogenetic features of human immunodeficiency virus-1 (HIV-1) infection in pregnancy and perinatal HIV infection, and to explore immunization strategies for preventing maternal-infant transmission of HIV. DATA SOURCES: MEDLINE data base and reference lists of articles were used to identify relevant papers. Reports from conferences were noted if the data had not yet been published. METHODS OF STUDY SELECTION: We reviewed all English-language papers pertaining to maternal or fetal infection with HIV, immunology of HIV infection, immunization of pregnant women, or immunization against HIV. DATA EXTRACTION AND SYNTHESIS: Human immunodeficiency virus infection of women is increasing, and vertical transmission of HIV to children is a growing problem. There is evidence for intrauterine, intrapartum, and immediate postpartum transmission, but it is thought that the majority of transmissions occur peripartum by a minor subset of the maternal HIV-1 strains. Diagnostic advances include measurement of HIV-specific immunoglobulin A (IgA) and improved systems for polymerase chain reaction and virus isolation from potentially infected infants. Clinical and immunologic correlates of transmission remain uncertain. CONCLUSIONS: The epidemiology of transmission must be determined in more diverse populations. The timing and pathogenesis of HIV transmission from infected mother to fetus require better description, and improved diagnostic tools are needed. Immunologic and mechanical determinants that prevent transmission in the majority of cases need to be identified more precisely. Clinical trials to evaluate active immunization of HIV-infected pregnant women with candidate AIDS vaccines will potentially help answer many of these questions.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network.

OBJECTIVE: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp 160) candidate vaccine in humans. SUBJECTS: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups. INTERVENTIONS: The subjects were randomly assigned to receive 40 or 80 micrograms of rgp 160, 10 micrograms of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540. MEASUREMENTS AND MAIN RESULTS: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months. No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum antibody responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-micrograms doses of rgp160 and were most commonly of weakly reactive intensity. Responses were first noted by Western blot after the second dose. They markedly increased in frequency after the third dose and declined over the next 12 to 18 months. The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 to 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%). Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time. CONCLUSIONS: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.

Adult↗
PubMed1991

Reinfection of mice with respiratory syncytial virus.

A BALB/c model of respiratory syncytial virus infection has been developed in which high-titered replication occurs in lung, immunological infiltrates in lung can be detected histologically, and illness can be consistently reproduced. The immunodeterminants of RSV reinfection in this system were investigated by rechallenging mice with RSV early (less than 2 months after primary infection) and late (16 to 21 months after primary infection) and correlating illness and titer of RSV isolated from lungs and noses with RSV-specific serological responses and lung histology. After early rechallenge, RSV was cleared within 24 hours from both nose and lung. After late rechallenge, RSV was isolated at 72 hours from nose in 21/24 mice, but from lung in only 5/24 mice. Isolation of RSV from lung after rechallenge was associated with low RSV-specific antibody titers measured by ELISA and plaque-reduction neutralization. The presence of lymphocyte aggregates around the bronchovascular bundles was associated with inability to isolate RSV from lung and lack of illness. The basophilic lymphocytes were small and uniform in size with dense nuclei and a small amount of cytoplasm. These studies demonstrate that nasal and pulmonary reinfection with RSV is possible in mice after late rechallenge. The studies also indicate the potential importance of RSV-specific antibody in protecting lung from reinfection.

Animals↗
PubMed1991

Clinical implications of resilient denture lining material research. Part II: Gelation and flow properties of tissue conditioners.

The clinical effectiveness of tissue conditioners and functional impression materials is influenced by their gelation and flow properties. Laboratory tests were previously conducted that simulated the conditions of clinical use to the extent possible on six commercial intraoral-gelling resilient denture liners. The liners were found to vary significantly in their gelation times and to flow throughout the 7-day study. Their initial flow after mixing was influenced most by the time of loading. While extrapolations to the clinical environment require caution, the results of this study imply that the dentist should (1) adapt clinical techniques to the gelation times of particular materials, (2) reduce the initial flow of some materials by delaying denture placement on the supporting mucosa, and (3) expect the materials to be effective tissue conditioners for at least 7 days.

Acrylic Resins↗
PubMed1991

In vivo fungal presence and growth on two resilient denture liners.

To determine whether two intraoral-setting resilient denture liners supported the in vivo presence or growth of oral commensal fungi, the liners were randomly placed in the mandibular complete dentures of 14 patients. Cytologic smears were made from the liner surfaces at 1 hour and 1, 2, 7, 14 and 30 days after intraoral placement. Yeast forms were observed in six patient trials of material A and in two trials of material B. Hyphae were observed in only one patient trial of material A and in two trials of material B. When yeast forms and hyphae findings were combined and were considered as indicative of fungal presence or growth, the prevalence up to 30 days was seven for material A and four for material B. Statistical analysis revealed no significant difference in the prevalence of fungal presence or growth between the two resilient denture liners tested.

Acrylic Resins↗
PubMed1991

Gel strength and rate of gelation of soft polymers.

A rheometer was used to characterize the gelation rate of six commercial short- to medium-term (chairside intra-oral gelation) denture soft-lining materials. Shear puncture force was measured from one to 60 days for six short- to medium-term materials as well as for three heat-cured (polymerizable) materials. The observed increase in puncture force with age of the specimen was considered to be a function of increased polymer chain entanglement and/or loss of plasticizer. Reduction in puncture force with age occurred for some materials as a result of hydration of the polymer gel. Rheometer setting time (gelation rate) and puncture force values for the intra-oral gelation materials were influenced by the quantity of ethyl alcohol present in the mixing liquid. In general, the higher the level of ethyl alcohol, the shorter the gelation time and the stronger the gel. The characterization of the properties may help develop improved prosthodontic treatment procedures, and allow better management of soft-tissue recovery following trauma.

Denture Liners↗
PubMed1991

Respiratory syncytial virus infection in anti-mu-treated mice.

BALB/c mice were depleted of B cells by anti-mu treatment to investigate the pathogenesis of respiratory syncytial virus (RSV) infection in the absence of antibody. Termination of RSV replication after primary infection occurred with the same kinetics in anti-mu-treated mice as in phosphate-buffered saline (PBS)-treated controls. Yet, when rechallenged, anti-mu-treated mice were more permissive to RSV replication than PBS-treated controls. Anti-mu-treated mice also experienced greater illness than PBS-treated controls during both primary infection and rechallenge. Passive transfer of RSV-specific immune serum to anti-mu-treated mice before rechallenge reconstituted complete protection from RSV replication and diminished illness. Thus, RSV-specific antibody is not required to terminate RSV replication in primary infection, but without antibody, only partial immunity against rechallenge is induced. While it is unknown whether the mechanism is a direct effect on RSV titer or modulation of the illness-causing cellular immune response, the presence of RSV-specific antibody reduces illness in both primary RSV infection and rechallenge of mice.

Animals↗
PubMed1991

Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice.

The role of CD4+ and CD8+ T lymphocytes in terminating respiratory syncytial virus (RSV) replication, causing disease, and protecting from reinfection was investigated using a BALB/c mouse model in which CD4+ or CD8+ lymphocytes or both were depleted by injections of Mab directed against the respective mouse lymphocyte determinants. Kinetics of RSV replication, illness, and pathology were assessed after primary infection and rechallenge. Both CD4+ and CD8+ lymphocyte subsets were involved in terminating RSV replication after primary infection. When both T lymphocyte subsets were depleted RSV replication was markedly prolonged, yet no illness was evident, suggesting that host immune response rather than viral cytocidal effect was the primary determinant of disease in mice. Both CD4+ and CD8+ lymphocytes contributed to illness, although CD8+ lymphocytes appeared to play the dominant role in this particular system. Analysis of histological responses suggested that CD4+ lymphocytes were required for the appearance of peribronchovascular lymphocytic aggregates seen in normal mice after rechallenge, and that the presence of alveolar lymphocytes was correlated with illness. It is postulated that antibody is an illness-sparing mechanism for protecting mice from RSV infection, and that T lymphocytes are an important determinant of illness. Further delineation of RSV-induced immunopathogenesis in primary infection and reinfection will provide important information for the development of vaccine strategies.

Animals↗
PubMed1991

An in vivo and in vitro study of the loss of plasticizer from soft polymer-gel materials.

Polymer-gel materials used as short-term denture soft linings are blended with plasticizers to lower the glass transition temperature (Tg). A lower Tg allows for greater polymer chain mobility, thus producing a more flexible material. The present work evaluated the loss of plasticizers due to leaching both in vivo and in vitro. Two commercial denture soft-lining materials (A and B) were tested. These were both poly(ethyl methacrylate) polymers, blended with alcohol and phthalate esters. A clinical study was conducted in which patients wore, sequentially, dentures bearing (on separate occasions) each of the two soft-polymer lining materials. The two materials A and B were randomly assigned for each of ten patients and were worn for 14 and 30 days, respectively. With one exception, patients wore dentures with both lining materials, for a total of 19 clinical evaluations. The plasticizer loss occurring during the clinical trial was determined by GC analysis from the initial and terminal day sampling of plasticizer content of the soft polymer-gel materials. The results of this analysis were compared with results obtained from an in vitro leachability study by use of sink conditions in water at 37 degrees C for the same two commercial soft polymers conducted over the same time periods of 14 and 30 days. The results indicated that a higher loss of plasticizer occurred in vivo, compared with the in vitro tests for 17 of the 19 clinical evaluations. The average plasticizer lost in vivo from material A at 14 days was 122 +/- 58 mg/g, and for material B at 30 days it was 33 +/- 27 mg/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗
PubMed1990

Growth of human cell lines in BALB/c mice.

A method of immunodepletion that allows the growth of xenogeneic cell lines in mice is described. Treatment of adult BALB/c mice with sublethal irradiation (400 total body rads) and CD4+ lymphocyte depletion renders them tolerant to the growth of human lymphocytic (CEM), monocytic (U937), and epithelial (HEp-2) cell lines. The system has also been used to generate ascites from rat hybridomas. The methodology is technically easy, inexpensive, and expedient and should have multiple uses in biomedical research including mouse modeling of human viral infections and investigation of transplant rejection.

Animals↗
PubMed1990

Clinical compliance of two resilient denture liners.

Although intra-oral-setting resilient denture liners have been used for 30 years to treat the severely resorbed residual ridges of elderly patients, their clinical physical properties are not well understood. The effect of clinical usage on the compliance (compressibility, flexibility) of two intra-oral-setting resilient denture liners was measured in 10 patients, for up to 30 days. The clinical compliance of Material B (Coe-Comfort) was found to be significantly greater than Material A (Veltec) for up to 14 days. At 24 h both materials had significant compliance reductions from the original 1 h measurement. These compliance reductions continued throughout the testing period. For up to 14 days of clinical usage there were no significant differences between the compliance reductions of the two materials. The study suggests that (i) Material B would provide more effective tissue conditioning of abused residual ridge mucosa than Material A; and (ii) a functional impression made with these materials should be left in the mouth for at least 24 h before the cast is poured.

Acrylic Resins↗
PubMed1990

Antifusion activity in sera from persons infected with human immunodeficiency virus type 1.

Cell-to-cell fusion plays an important role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infections. An assay to measure the antifusion activity of serum has been developed by using the fusion event that occurs between H9 cells chronically infected with HIV-1 (H9IIIB) and fusion-susceptible MT-2 cells. The endpoint is determined by measuring neutral red uptake in cells after syncytium formation is allowed to occur in the presence of various serum dilutions. The assessment of antifusion activity in serum by neutral red uptake has been shown to correlate with syncytium reduction as determined by direct counting. The optimal number and ratio of cells in the suspension for efficiency and speed of the assay have been determined. With this assay it was shown that 50% of 36 serum specimens capable of neutralizing cell-free virions failed to inhibit syncytium formation. The assay can thus measure a distinct activity in HIV-1-immune human sera which is a subset of neutralization activity. Because of the potential role of this activity in the rate of disease progression and protective immune responses, the antifusion assay will be an important tool for the investigation of disease pathogenesis and for acquired immunodeficiency syndrome vaccine development. The assay can also be applied to the investigation of the pathogenesis of the fusion event at the cellular level. The ability to use absorbance measurements rather than syncytium counts as the endpoint facilitates direct computer-assisted data analysis, which expedites the performance of the assay.

Cell Fusion↗
PubMed1990

Development of an AIDS vaccine. Biological and ethical challenges.

The biologic, ethical, and social obstacles in AIDS vaccine development are explored. Current understanding of the immunodeterminants of HIV-1 pathogenesis is reviewed and ideal biological properties for an AIDS vaccine are proposed. Options for clinical trial design, criteria for entry into clinical trials, and provision for care of volunteers who experience vaccine-associated adversity are discussed.

Acquired Immunodeficiency Syndrome↗